UCSF HELEN DILLER FAMILY COMPREHENSIVE CANCER...

American Association for Cancer Research Annual Meeting

UCSF HELEN DILLER FAMILY COMPREHENSIVE CANCER CENTER

April 16-20, 2016New Orleans, LAUCSF Presentation Brochure

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As president of the UCSF Helen Diller Family Comprehensive Cancer

Center, one of my key priorities is to initiate and advance programs

that are developing new anticancer drugs making significant impact

on helping cancer patients live longer and better lives. I recognize this

goal is best accomplished by working in partnership with the broader

life science industry. This searchable abstract book of UCSF research

presented at AACR is a resource for potential partners interested in

identifying world-class faculty engaged in basic science and clinical

oncology research.

As an NCI-designated comprehensive cancer center, UCSF is

recognized for our outstanding science, extensive resources, depth

and breadth of our research in basic, clinical, and/or population

sciences, as well as cutting edge research that bridges these

scientific areas. Practically this means that our clinicians and basic

scientists work closely together to (1) identify, develop and optimize

novel therapeutics for biological efficacy and clinical utility, (2) assess

tumor status and responsiveness to current therapies, (3) develop

biomarkers for patient stratification and therapeutic response and (4)

advance supportive care options to mitigate the toxicities associated

with chemotherapy.

UCSF is home to many of world’s finest oncology scientists and

clinicians. I invite you learn more about our work and expertise by

reaching out to our faculty. If you have any additional questions or

need any assistance with your outreach, please contact the Director

of Strategic Alliances for the Cancer Center: Cammie Edwards

( ).

Wishing you a very productive meeting and we look forward to

future discussions and collaborations.

Alan Ashworth, PhD, FRSPresident, UCSF Helen Diller Family Comprehensive Cancer Center

Committed to Advancing Development of Improved Cancer Therapies, Imaging Modalities, and Biomarkers

Alan Ashworth, PhD, FRSPresident, UCSF Helen Diller Family Comprehensive Cancer Center

Senior Vice President for Cancer Services, UCSF Health

Professor of Medicine, Division of Hematology/Oncology, Department of Medicine

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The “comprehensive” designation—NCI’s highest ranking, awarded only after a rigorous evaluation process—recognizes UCSF’s excellence in basic research, clinical research, population based research, outreach and education, and our ability to integrate these diverse research approaches to cancer and turn them into clinical practice.

A Designated NCI Comprehensive Cancer Center Since 1999

HDFCCC Overview

Our Success is Driven by Our FacultyHDFCCC Membership: 397 Members & Associate Members2 Nobel Laureates

3 Albert Lasker Award winners

8 Howard Hughes Medical Investigators

13 Members of the National Academy of Sciences

20 Members of the Institute of Medicine

18 Fellows of the American Academy of Arts and Sciences

4 Fellows of the Royal Society

Working Together Advancing the Understanding and Treatment of Cancer

HDFCCC Overview

Translating Laboratory Discoveries into Improved Patient CareWhether it is advancing a new vaccine based immunotherapy, developing a new diagnostic test to distinguish benign moles from malignant melanoma or pioneering new adaptive clinical trial designs, UCSF success in translating laboratory discoveries into improved patient care comes from its faculty and culture of exploration and collaboration. With over 400 faculty relentlessly pursuing oncology research and clinical practice, we continue to make significant strides in understanding the biology of disease and improving patient outcomes with advanced clinical care.

Multi-Disciplinary Research Programs• Breast Oncology

• Cancer Control

• Cancer Genetics

• Cancer, Immunity, and Microenvironment

• Developmental Therapeutics

• Hematopoietic Malignancies

• Neurologic Oncology

• Pediatric Malignancies

• Prostate Cancer

• Tobacco Control

Key Initiatives• Cancer Imaging

• Cancer Immunotherapeutics

• Global Oncology

• Center for BRCA Research

• UCSF 500

• Target Validation Initiative

Multi-Disciplinary Clinical Programs • GU Oncology (non Prostate)

• GI (includes Pancreas Cancer)

• Thoracic Oncology

• Cutaneous Oncology

• Head and Neck Cancer

• Sarcoma

• Endocrine

• Gynecologic Oncology

• Breast Oncology

• Prostate Cancer

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• Biostatistics

• Clinical Research Support

• Genome Analysis

• Laboratory for Cell Analysis

• Immunohistochemistry & Molecular Pathology

• Mouse Pathology

• Preclinical Therapeutic Testing

• Bio-specimen Banking

• Tobacco Biomarkers

• Bioinformatics

• Computational Biology

UCSF consistently ranks among

the top U.S. biomedical research

organizations in cancer-specific

federal funding. In 2015, UCSF

received more than $85M from the

National Cancer Institute.

HDFCCC Overview

Core Capabilities Supporting Our Programs

Approximately one-quarter of the

University’s ~2,200 full-time faculty

members work in cancer research or

cancer care.

UCSF faculty have a long history of working with industry partners translating discoveries into products that ultimately improve patient care. We are experienced in establishing and executing on a wide range of successful partnerships. If you are interested in learning more about working with the HDFCCC and its faculty, please contact:

Cammie Edwards, PhDDirector of Strategic Alliances, HDFCCC

• On average, UCSF has 200-300 new invention disclosures per year

• An estimated 90 life science start-up companies have been spawned from the University’s labs, including Genentech, Chiron, and Intellikine

• Included among UCSF patents are top revenue producers, such as

UCSF IN THE NEWS (Click on title to read story)

Partnering with UCSF HDFCCC

AACR Elects UCSF’s Alan Ashworth and Jennifer Grandis to Board of Directors, Nominating Committee http://cancer.ucsf.edu/news/2016/04/11/american-association-for-cancer-research-elects-ucsf-faculty-to-board-of-directors-nominating-committee.7420

VP Biden Discusses Cancer Moonshot with UCSF Expertshttp://cancer.ucsf.edu/news/2016/03/02/vp-biden-discusses-cancer-moonshot-with-ucsf-experts.7355

BRCA Clinics Expand Further Beyond Breast Cancer: New thinking on pancreatic, prostate cancer treatment; centers consolidate patient care under one roofhttp://cancer.ucsf.edu/news/2016/02/22/brca-clinics-expand-further-beyond-breast-cancer.7315

UCSF Establishes Quantitative Biosciences Institute: New Research Unit will Identify Opportunities for Disease Treatments Using Computation, Mathematics and Statisticshttp://cancer.ucsf.edu/news/2016/03/17/ucsf-establishes-quantitative-biosciences-institute.7376

UCSF Research Suggests New Model for Cancer Metastasis: Imaging Catches Cancer Cells in the Act As They Recruit Immune Cells to Spread Diseasehttp://cancer.ucsf.edu/news/2016/03/17/ucsf-research-suggests-new-model-for-cancer-metastasis.7374

Melanoma’s Genetic Trajectories Are Charted in New Study: Study Confirms ‘Intermediate’ Disease Stage Between Benign Moles and Malignancyhttp://cancer.ucsf.edu/news/2015/11/12/melanomas-genetic-trajectories-are-charted-in-new-study.6907

- Hepatitis B vaccine

- Bovine growth hormone

- Barrier repair lipids

- Yeast expression vector

- Magnetic resonance imaging

http://cancer.ucsf.edu/news/2016/04/11/american-association-for-cancer-research-elects-ucsf-faculty-to-board-of-directors-nominating-committee.7420

cancer.ucsf.edu/news/2016/03/02/vp-biden-discusses-cancer-moonshot-with-ucsf-experts.7355

cancer.ucsf.edu/news/2016/03/02/vp-biden-discusses-cancer-moonshot-with-ucsf-experts.7355

cancer.ucsf.edu/news/2016/02/22/brca-clinics-expand-further-beyond-breast-cancer.7315

cancer.ucsf.edu/news/2016/02/22/brca-clinics-expand-further-beyond-breast-cancer.7315

cancer.ucsf.edu/news/2016/03/17/ucsf-establishes-quantitative-biosciences-institute.7376



cancer.ucsf.edu/news/2016/03/17/ucsf-research-suggests-new-model-for-cancer-metastasis.7374

cancer.ucsf.edu/news/2016/03/17/ucsf-research-suggests-new-model-for-cancer-metastasis.7374

cancer.ucsf.edu/news/2015/11/12/melanomas-genetic-trajectories-are-charted-in-new-study.6907

cancer.ucsf.edu/news/2015/11/12/melanomas-genetic-trajectories-are-charted-in-new-study.6907

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Presentations

*UCSF authors in bold

Presentations

E-cigarettes: Expanding the Nicotine EpidemicAuthors*: Lauren Dutra

Pres #: Section: Presentation Date/Time: Sunday, April 17: 3:00-4:30PM

Location: Room 283 Presentation Type: Science Policy Session Lauren Dutra Expertise: Lauren Dutra’s research interests include disparities in smoking and smoking-related disease, the targeted marketing of vulnerable populations by tobacco companies, and new tobacco products, such as e-cigarettes. She has a Doctor of Science from the Harvard School of Public Health and is a Social Epidemiologist by training. Her dissertation focused on experiences of injustice and smoking behavior in South Africa and the US.

Prior to obtaining her doctorate, she received a Masters in Mental Health and Behavioral Medicine from Boston University and worked as a psychotherapist/health behavior counselor. Lauren has first-author publications in Social Science & Medicine, JAMA Pediatrics, and Tobacco Control, as well as publications in Preventive Medicine, Diabetes Care, and the Journal of Cognitive Psychology.

http://profiles.ucsf.edu/lauren.dutra

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MEK and PI3K signaling cooperate through mTORC1/2 to promote PIK3CA mutant melanoma cell proliferationAuthors*: Jillian M. Silva, Marian M. Deuker, Bruce C. Baguley, Martin McMahon

Pres #: 29 Section: 1 Presentation Date/Time: Sunday, April 17: 1:00-5:00PM

Location: Presentation Type: Poster Session Silva Lab Expertise: The overarching goal of the Silva lab research is to understand the underlying molecular and biochemical mechanisms of cooperation between key signaling networks, such as MAPK and PI3K, that are essential for carcinoma maintenance and to identify potential molecular targets that could contribute to the development of pathway-targeted therapy for cancer patients. We use cutting-edge screening technologies, such as a lentiCRISPR-Cas9 knockout library and ribosome profiling, along with genetic/pharmacological inhibitory strategies and xenograft tumor models to dissect out the these key kinase mechanisms and the consequences of their inhibition. Melonoma is our primary model system, but we apply our discoveries to other types of cancer that share similar molecular and biochemical landscapes. http://profiles.ucsf.edu/jillian.silva

View full abstracts on line at: http://www.abstractsonline.com/plan/start.aspx?mkey=%7b1D10D749-4B6A-4AB3-BCD4-F80FB1922267%7d


http://www.abstractsonline.com/plan/start.aspx?mkey=%7b1D10D749-4B6A-4AB3-BCD4-F80FB1922267%7d

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Presentations


Identification of new therapeutic targets and molecular predictors of response in oesophageal cancer Authors*: Irene Chong, lauren Aronson, David Cunningham, James Campbell, Colm Ryan, Michael Davidson, Ian Chau, Alan Ashworth, Christopher J. Lord


Location: Presentation Type: Poster Session

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Functional effects of MutL homolog 1 promoter polymorphisms in prostate cancer Authors*: Shinichiro Fukuhara, Yozo Mitsui, Yutaka Hashimoto, Taku Kato, Ryan K. Wong, Varahram Shahryari, Soichiro Yamamura, Shahana Majid, Sharanjot Saini, Guoren Deng, Rajvir Dahiya, Yuichiro Tanaka


Location: Presentation Type: Poster Session Tanaka Lab Expertise: The Tanaka lab’s research focuses on genetic risk factors for urological cancers, their effects within the cell, as well as the functional role of various genes at the cellular and molecular levels. They have shown that variable expression between isoforms of estrogen, progesterone and androgen receptors in prostatic carcinogenesis and that inactivation is due to CpG methylation. They have identified genetic polymorphisms shown to be risk factors for prostate & kidney cancers and have examined genetic alterations in the estrogen-related pathway. They have also found a race-specific polymorphism in the coding region of the MLH1 DNA repair gene that confers protection from prostate cancer among a Japanese population.

https://www.ncire.org/research/researchers_by_name/Yuichiro-Tanaka-PhD/

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Presentations


Whole exome and targeted deep sequencing identify genome-wide allelic loss and frequent SETDB1 mutations in malignant pleural mesotheliomas

Authors*: Hio Chung Kang, Hong Kwan Kim, Sharon Lee, Pedro Mendez, James Kim, Gavitt Woodard, Kuang-Yu Jen, Li Tai Fang, Kirk Jones, David Jablons, Il Jin Kim


Location: Presentation Type: Poster Session Kim Lab Expertise: Dr. Il-Jin Kim has focused his career on three important cancer-related areas: 1) cancer genetics and genomics, 2) early detection and 3) cancer prevention. Dr. Kim has published approximately 70 papers in these areas. He has also been granted three patents for mutation detection methods. Projects in these areas include: genetic screening in hereditary (familial) cancers to distinguishing carriers from non-carriers, development of new genetic screening methods for cancer prevention, and genome-wide gene expression microarray analysis.

Current projects in the Kim Lab include: Cancer Genetics and Genomics, Early Detection, Cancer Prevention. http://kimlab.surgery.ucsf.edu/about-us.aspx

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Investigating microtubule growth dynamics in patient-derived metastatic prostate cancer cellsAuthors*: Alexandre Matov, Johan de Rooij, Jay Gatlin, Julia Rohrberg, Nikta Ahmad, Rahul Aggarwal, Jeff Simko, Andrei Goga, Charles Ryan, Torsten Wittmann


Location: Presentation Type: Poster Session Wittman Lab Expertise: The Wittmann lab aims to elucidate molecular mechanisms by which polarity of intracellular cell biological processes – such as cytoskeleton dynamics or vesicular transport – controls complex behavior and function of mammalian cells. We are specifically interested in the function & dynamics of the microtubule cytoskeleton & a diverse group of +TIP proteins that associate with growing microtubule ends. In addition to molecular biology & biochemistry, we use advanced quantitative fluorescence microscopy. We are also interested in how deregulation of intracellular microtubule dynamics contributes to cancer pathology and resistance to microtubule targeting agents, and if this can be used to predict drug response. Finally, we also develop novel ‘opto-cell biology’ to interfere with intracellular protein function at high spatial & temporal resolution by using plant-derived light-sensitive protein domains.

http://wittmann.ucsf.edu/

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Presentations


Cotargeting EGFR, STAT3 and Src-Notch pathways: a promising approach to improve the efficacy of EGFR-TKIs in the treatment of NSCLC patients

Authors*: Niki Karachaliou, Imane Chaib, Sara Piloeo, Jordi Codony, Xueting Cai, Xuefei Li, Ana Drozdowskyj, Carles Codony, Andrés Felipe Cardona, Guillermo López-Vivanco, Alain Vergnenègre, José Miguel Sánchez, Mariano Provencio, Filippo de Marinis, Enric Carcereny, Noemí Reguart, Rosario García-Campelo, Silvia Marin, Cristina Teixidó, Isabella Sperduti, Sonia Rodríguez, Roger Estrada, Raimon Puig de la Bellacasa, José Luis Ramírez, Miguel Angel Molina-Vila, Caicun Zhou, Peng Cao, Patrick Ma, Trever Bivona, Rafael Rosell.



Bivona Lab Expertise: Our team uses the tools of precision medicine to improve the molecular diagnosis and targeted therapy of patients with solid cancers, including lung cancer. Our program focuses on identifying and functionally characterizing the molecular drivers of tumor growth in individual patients. We study patient samples and clinical data to identify novel potential drivers of tumor initiation, progression, and therapy resistance. We functionally annotate the putative molecular drivers using an integrated approach of genetic and pharmacologic tools. This precision approach to understanding the molecular pathogenesis of lung cancer (and other cancers) has led to the discovery of new biomarkers and targets that provide rationale for novel clinical trials we are launching to improve patient survival.

http://www.bivonalab.net/

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EGFR inhibition generates drug tolerant persister cells by blocking AKT activity and thus inactivating Ets-1 function

Authors*: Janyaporn Phuchareon, David W. Eisele, Frank McCormick, Osamu Tetsu


Location: Presentation Type: Poster Session Tetsu Lab Expertise: The Tetsu Laboratory is interested in the mechanisms underlying initiation and progression of various malignancies originated from endoderm; lung, colon and pancreatic cancers. They have exploited the cell signaling pathways that make the cancers different from normal tissues. More recently, their research interests have focus on drug resistance to EGFR and Ras inhibitors. In order to establish truly effective treatments, they have proposed a multi-drug combination therapy targeting the origin of acquired resistant cells, as reduction of this subset may prevent emergent resistance to the kinase inhibitors. In this era of precision medicine, they intend to design the most relevant combination to overcome the patient-specific drug resistance.

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Presentations


SRC mediates intrinsic resistance to BRAF(V600E) inhibition in colon cancerAuthors*: Jean-Philippe F. Coppé, Changjun Wang, Diede Brunen, Anirudh Prahallad, Ana Ruiz-Saenz, Danislav Spassov, Bo Pan, Aleksandra Olow, Denise Wolf, Christina Yau, Christian Posch, Evelyn Lee, Miki Mori, Katherina Chua, Julia Malato, Donghui Hwang, Paul Phojanakong, Zhongzhong Chen, Byron Hann, Lamorna Brown-Swigart, Mark Moasser, René Bernards, Laura van ‘t Veer


Location: Presentation Type: Poster Session van ‘t Veer Lab Expertise: Dr. van ’t Veer’s research focuses on personalized medicine & advancing patient management based on knowledge of the genetic makeup of the tumor as well as the genetic makeup of the patient. Her laboratory investigates human kinases & how kinase inhibitors elicit response & resistance, which is also utilized to understand agent efficacy in the I-SPY 2 TRIAL. She is the PI of the Athena Breast Health Network, a 150,000 women cohort study evaluating new paradigms to enhance breast health. She leads the targeted genome testing of 100,000 women for 9 breast cancer susceptibility genes and a selection of ~100 known susceptibility SNPs. She is one of the PIs for the NIH Big Data to Knowledge Center Translational Genomics, facilitating worldwide standardization of sharing annotated genomics data.

http://cancer.ucsf.edu/people/profiles/vantveer_laura.3358

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Pathway-directed high throughput drug screen identifies PI3K inhibitors that synergistically potentiate anti-tumor activity of HDAC inhibitors in mycosis fungoides and Sézary syndromeAuthors*: Chen-Yen Yang, Razan Faraj, Taha Rakhshandaroo, Shervin Afghani, Laura Pincus, Sourav Bandyopadhyay, Frank McCormick, Weiyun Ai



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Presentations


NTF2 regulates nuclear size in mammalian cells and may contribute to altered nuclear size in melanoma Authors*: Lidija D. Vukovic, Bradley A. Stohr, Dan L. Levy


Location: Presentation Type: Poster Session Stohr Lab Expertise: The research in my laboratory focuses on the telomere biology of human cancers. Telomeres are nucleoprotein structures that protect the ends of linear chromosomes. Telomeres shorten with each cell division, ultimately resulting in deprotection of the chromosome ends. Telomeric deprotection serves a tumor-suppressive function by initiating senescence and/or apoptosis in inappropriately dividing cells. However, deprotected telomeres frequently fuse together, resulting in genome instability that can promote tumorigenesis. The cellular context determines whether it is the tumor-suppressive or tumor-promoting role of the dysfunctional telomere that predominates. The long-term goal of my laboratory is to understand how different types of telomere dysfunction provoke these diverse cellular responses. This knowledge will provide insight into the origins and progression of human cancers and suggest novel strategies for telomere-based therapeutic approaches.

http://labmed.ucsf.edu/about/faculty/pathology-bstohr.html

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Novel and shared neoantigen for glioma T-cell therapy derived from histone 3 variant H3.3 K27M mutation

Authors*: Hideho Okada, Gary Kohanbash, Kaori Okada, Shuming Liu, Yi Lin, Sabine Mueller, Ian F. Pollack, Angel M. Carcaboso, Yafei Hou


Location: Presentation Type: Poster Session Okada Lab Expertise: As a translational physician scientist, Dr. Okada and his lab are focused on development of novel immunotherapeutic strategies for brain tumor patients. For example, Dr. Okada conducted one of the first immune gene therapy trials in patients with malignant glioma. His lab was also the first to identify and fully characterized cytotoxic T-lymphocyte epitopes for gliomas. Dr. Okada has also delineated the role of an integrin receptor very late activation antigen-4 and chemokine CXCL10 in efficient trafficking of T-cells to brain tumor sites. Dr. Okada has integrated these findings to develop a number of vaccine trials in both adult and pediatric glioma patients. More recently, his group developed a novel chimeric antigen receptor targeting glioblastoma cells, and are currently conducting a pilot trial.

http://neurosurgery.ucsf.edu/index.php/about_us_faculty_okada.html

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Presentations


Deregulated Myc is an immunosuppressive switch Authors*: Roderik M. Kortlever, Nicole M. Sodir, Catherine H. Wilson, Deborah L. Burkhart, Lamorna Swigart, Trevor D. Lielewood, Gerard I. Evan



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Establishment and characterization of a panel of cell-based and patient-derived chordoma tumor models Authors*: Michael J. Wick, Melissa Rundle, Lizeee Gamez, Armando Diaz, Josh Sommer, Patricia Cogswell, Byron Hann, Joanna Phillips, Kyriakos P. Papadopoulos


Location: Presentation Type: Poster Session Phillips Lab Expertise: Our laboratory is focused on understanding how invading brain tumor cells interact with the components of the tumor microenvironment, and how these key interactions influence glioma initiation, progression, and invasion. We use both in vivo and ex vivo model systems to study the interaction between tumor cells and the microenvironment including microglia, macrophages, reactive astrocytes, and the extracellular matrix. These studies will hopefully lead to the identification of novel therapeutic targets. In addition, using primary human brain tumors we are investigating potential diagnostic and prognostic brain tumor biomarkers.

https://bms.ucsf.edu/directory/faculty/joanna-j-phillips-md-phd

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Nanoliposomal targeting of Ephrin receptor A2 (EphA2): Clinical translationAuthors*: Walid S. Kamoun, Shinji Oyama, Tad Kornaga, Theresa Feng, Lia Luus, Minh T. Pham, Dmitri B. Kirpotin, James D. Marks, Melissa Geddie, Lihui Xu, Alexey A. Lugovskoy, Monica Murphy, Carl Morrisson, Daryl C. Drummond



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Presentations


Interaction between meat and fish intake and genes involved in hormones, inflammation and energetic factors, and risk of breast cancer among Hispanic and Non-Hispanic White women: The Breast Cancer Health Disparities Study Authors*: Andre E. Kim, Juan Pablo Lewinger, Shirong Zhang, Roger K. Wolff, Laura Fejerman, Esther M. John, Gabriela Torres-Mejia, Jennifer S. Herrick, Stephanie D. Boone, Avonne E. Connor, Lisa M. Hines, Kathy B. Baumgartner, Anna Giuliano, Martha L. Slaeery, Mariana C. Stern


Location: Presentation Type: Poster Session Fejerman Lab Expertise: Dr. Fejerman focuses on the discovery of genetic and non-genetic factors that contribute to breast cancer risk and prognosis in Latinas. Her past work established a relationship between genetic ancestry and breast cancer risk, where higher European ancestry in U.S. and Mexican Latinas was associated with an increased risk. Her subsequent research has built upon this observation, exploring genetic variants, through admixture mapping and genome-wide association approaches, as well as the possible environmental and lifestyle related factors, and ancestry-gene interactions. Recent work explores disparities in breast cancer prognosis by genetic ancestry in Latinas and its potential causes.

http://fejerman.ucsf.edu

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Combining sensitivity markers to identify triple-negative breast cancer patients most responsive to veliparib/carboplatin: results from the I-SPY 2 TRIAL Authors*: Denise M. Wolf, Christina Yau, Ashish Sanil, Larmorna Brown-Swigart, Gillian Hirst, Meredith Buxton, Melissa Paolini, Olufunmilayo Olopade, Hope Rugo, Angela De Michele, Fraser Symmans, Don Berry, Laura Esserman, Laura van ‘t Veer

Pres #: 858 Section: Presentation Date/Time: Sunday, April 17: 5:35-5:50PM

Location: Room 391 Presentation Type: Minisymposium van ‘t Veer Lab Expertise: Dr. van ’t Veer’s research focuses on personalized medicine & advancing patient management based on knowledge of the genetic makeup of the tumor as well as the genetic makeup of the patient. Her laboratory investigates human kinases & how kinase inhibitors elicit response & resistance, which is also utilized to understand agent efficacy in the I-SPY 2 TRIAL. She is the PI of the Athena Breast Health Network, a 150,000 women cohort study evaluating new paradigms to enhance breast health. She leads the targeted genome testing of 100,000 women for 9 breast cancer susceptibility genes and a selection of ~100 known susceptibility SNPs. She is one of the PIs for the NIH Big Data to Knowledge Center Translational Genomics, facilitating worldwide standardization of sharing annotated genomics data.


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Presentations


BRM loss promotes tumor progression through extracellular matrix remodeling and elevated mammary epithelial stem/progenitor activityAuthors*: Jason J. Northey, Laura Damiano, Valerie M. Weaver

Pres #: 911 Section: Presentation Date/Time: Sunday, April 17: 4:50-5:05PM

Location: Room 393 Presentation Type: Minisymposium Weaver Lab Expertise: The extracellular matrix (ECM), the noncellular component of the microenvironment, influences cell growth, survival, migration and tissue-specific differentiation through a repertoire of cellular receptors including integrins, syndecans and discoidin receptors. We are exploring the molecular mechanisms whereby these ECM receptors modulate cell fate: specifically, how mechanical and topological properties of the matrix, which are related to its composition and organization, regulate the function of matrix receptors to alter cell behavior. Our research program is broadly divided into two fields of inquiry: (1) how matrix composition and organization influences mammary tissue development and tumor progression and (2) to clarify the role of matrix force on embryonic and adult stem cell fate.

http://weaverlab.ucsf.edu

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Anticancer effects of silibinin-induced small nucleolar RNA 11B on bladder cancer cellsAuthors*: Soichiro Yamamura, Yozo Mitsui, Shahana Majid, Hannah Nip, Nathan Bucay, Sharanjot Saini, Guoren Deng, Varahram Shahryary, Rajvir Dahiya, Yuichiro Tanaka

Pres #: 956 Section: 2 Presentation Date/Time: Monday, April 18: 8:00AM-12:00PM



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Presentations


Tumor suppressive role of a novel microRNA at frequently deleted chromosomal locus 8p21 in prostate cancerAuthors*: Nathan Bucay, Kiran Sekhon, Shahana Majid, Varahram Shahryari, Soichiro Yamamura, Z. Laura Tabatabai, Kirsten Greene, Yuichiro Tanaka, Rajvir Dahiya, Guoren Deng, Sharanjot Saini


Location: Presentation Type: Poster Session Saini Lab Expertise: The Saini lab focuses primarily on understanding the molecular basis of progression and metastasis of prostate cancer, in particular the role of microRNA (miRNA) genes located at frequently deleted genomic regions in prostate cancer epithelial-to mesenchymal transition (EMT), recurrence and metastasis. A role for miRNAs that affects EMT and progression and metastasis of human cancers has begun to emerge and Dr. Saini’s research provided initial evidence that miR-203 regulates EMT by directly targeting ZEB2 and other EMT regulators that in turn regulate PCa invasion and metastasis. Her recent research has identified additional novel miRNAs in prostate cancer that play an important role in prostate cancer EMT, recurrence and metastasis.

https://www.ncire.org/research/researchers_by_name/Sharanjot-Saini-PhD/

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Inhibitory effect of CYP1B1 on antitumor activities induced by dysregulated CDC20 and DAPK1 in renal cell carcinoma Authors*: Yozo Mitsui, Inik Chang, Shinichiro Fukuhar, Hiroshi Hirata, Ryan Kenji Wong, Soichiro Yamamura, Varahram Shahryari, Guoren Deng, Saini Sharanjot, Shahana Majid, Hiroaki Shiina, Rajvir Dahiya, Yuichiro Tanaka




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Presentations


HER3 is a functional molecular target in HPV-associated head and neck cancer Authors*: Toni Michel Brand, Stefan Hartmann, Neil Bhola, Noah D. Peyser, Hua Li, Yan Zeng, Max V. Randall, Sourav Bandyopadhyay, Jennifer R. Grandis


Location: Presentation Type: Poster Session Grandis Lab Expertise: We harness the power of genetic analyses to elucidate the genetic and epigenetic underpinnings of HNSCC with the goal of developing predictive biomarkers for molecular therapies. (HPV)16 plays an etiologic role in a growing subset of HNSCCs, where viral expression of the E6 and E7 oncoproteins are necessary for tumor growth and maintenance. We identified differential receptor tyrosine kinase (RTK) signaling in HPV(+) vs. HPV(-) tumors. One such RTK, HER3, is overexpressed and highly associated with phosphoinositide 3-kinase (PI3K) in HPV(+) tumors. Further investigation indicated that HPV(+) HNSCC cells were reliant on HER3 for cellular proliferation and PI3K pathway signaling, whereas little effect was observed in HPV(-) cell lines. These studies identify HER3 as a potential therapeutic target, and provide a rationale for the clinical evaluation of combined HER3 and PI3K inhibition in HPV(+) HNSCCs.

http://ohns.ucsf.edu/jennifer-grandis

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RRx-001 is effective in temozolomide-sensitive and resistant GBM Authors*: Veronica Steri, Bryan Oronsky, Jan Scicinski, Gabriele Bergers


Location: Presentation Type: Poster Session Bergers Lab Expertise: The Bergers laboratory focuses on revealing the dialogue between the tumor cell compartment and the vascular niche, of which the vasculature is an integral component. The vascular niche consists of distinct cell types and specialized matrices that provide signals controlling stem cell proliferation, fate specification, and protection in not only normal tissue, but tumors, as well. The long-term goal of Dr. Bergers’ research is to conduct a comprehensive investigation that defines the heterotypical signals of the tumor-host dialogue in the vascular niche in regulating neovascularization, stem cell maintenance, and tumor invasion during tumor progression and therapeutic resistance.

http://neurosurgery.ucsf.edu/index.php/research_BTRC_bergers.html

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Presentations


P32-targeting TT1 peptide delivers nanoparticles to intracranial glioblastomasAuthors*: Pille Säälik, Hedi Hunt, Allan Tobi, Anne-Mari Anton Willmore, Kadri Toome, Shweta Sharma, Ramana Kotamraju, Gabriele Bergers, Rolf Bjerkvig, Erkki Ruoslahti, Tambet Teesalu, Tambet Teesalu


Location: Presentation Type: Poster Session Bergers Lab Expertise: The Bergers laboratory focuses on revealing the dialogue between the tumor cell compartment and the vascular niche, of which the vasculature is an integral component. The vascular niche consists of distinct cell types and specialized matrices that provide signals controlling stem cell proliferation, fate specification, and protection in not only normal tissue, but tumors, as well. The long-term goal of Dr. Bergers’ research is to conduct a comprehensive investigation that defines the heterotypical signals of the tumor-host dialogue in the vascular niche in regulating neovascularization, stem cell maintenance, and tumor invasion during tumor progression and therapeutic resistance.


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Identification of the functional significance of mutations using the novel precision cancer analysis system

Authors*: Gabi Tarcic, Nir Peled, Zohar Barbash, Naama Barabash-Katzir, Shlomo Yaakobi, Naama Barabash-Katzir, Hani Nevo, Michael Vidne, Mariusz Adamek, Mordechai R. Kramer, Nikolai Goncharenko, Yakov Fellig, Karen Meir, Keith Mostov, Yoram Altschuler


Location: Presentation Type: Poster Session Mostov Lab Expertise: The Mostov laboratory studies epithelial morphogenesis and polarity in several organs including the liver. One of our interests is the mechanism by which cholangiocytes differentiate from hepatoblasts and progress to form ductal plates and eventually branching tubular networks. We recently developed a culture system in which a liver progenitor cell line, HPPL, reorganizes from a monolayer to tubular structures by being overlaid with a gel containing type I collagen and Matrigel. HPPL assumed a double layer configuration in the specialized culture environment and then developed a luminal space. Formation of the double layer does not involve cholangiocyte proliferation, but is associated with phosphatidylinositol 3-kinase and Akt activity, as well as transcriptional activity of HNF1.

http://mostovlab.ucsf.edu/Mostov_Lab_Website/Welcome.html

19

Presentations


MicroRNA-466 regulates bone metastasis by targeting RUNX2 in prostate cancerAuthors*: Shahana Majid, Hanna Nip, Altaf A. Dar, Sharanjot Saini, Varahram Shahryari, Soichiro Yamamura, Yozo Mitsui, Nathan Bucay, Guoren Deng, Rajvir Dahiya, Yuichiro Tanaka




__________________________________________________________________________

Body size and incidence of TMPRSS2:ERG fusion-positive and fusion-negative prostate cancerAuthors*: Thomas Ahearn, Rebecca E. Graff, Andreas Peeersson, Claire Pernar, Sarah C. Markt, Kathryn M. Wilson, Michelangelo Fiorentino, Massimo Loda, Edward L. Giovannucci, Lorelei A. Mucci


Location: Presentation Type: Poster Session Witte Lab Expertise: Our research program encompasses a synthesis of methodological and applied genetic epidemiology, with the overall aim of deciphering the mechanisms underlying complex diseases and traits (Witte, Visscher & Wray, Nature Reviews Genetics 2014). Our methods work is focused on the design and statistical analysis of next-generation sequencing and genetic association studies. We are applying these methods to studies of cancer (e.g., of the prostate), birth defects, and pharmacogenomics.

http://wittelab.ucsf.edu/pages/research

20

Presentations


Primary analysis of the EORTC 10041/ BIG 3-04 MINDACT study: A prospective, randomized study evaluating the clinical utility of the 70-gene signature (MammaPrint) combined with common clinical pathological criteria for selection of patients for adjuvant chemotherapy in breast cancer with 0 to 3 positive nodesAuthors*: Martine Piccart, Emiel Rutgers, Laura van’ t Veer, Leen Slaets, Suzette Delaloge, Giuseppe Viale, Jean Yves Pierga, Peter Vuylsteke, Etienne Brain, Suzan Vrijaldenhoven, P. Neijenhuis, Bruno Coudert, Tineke Smilde, Miguel Gil, Alastair Thompson, Isabel Rubio, Rodolfo Passalaqua, Erika Matos, Urlike Nitz, Mauro Delorenzi, Geraldine Thomas, Theodora Goulioti, Carolyn Straehle, Konstantinos Tryfonidis, Jan Bogaerts, Fatima Cardoso

Pres #: CT039 Section: Presentation Date/Time: Monday, April 18: 10:30-10:50AM

Location: La Nouvelle Orleans Ballroom Presentation Type: Clinical Trials Plenary Session

van ‘t Veer Lab Expertise: Dr. van ’t Veer’s research focuses on personalized medicine & advancing patient management based on knowledge of the genetic makeup of the tumor as well as the genetic makeup of the patient. Her laboratory investigates human kinases & how kinase inhibitors elicit response & resistance, which is also utilized to understand agent efficacy in the I-SPY 2 TRIAL. She is the PI of the Athena Breast Health Network, a 150,000 women cohort study evaluating new paradigms to enhance breast health. She leads the targeted genome testing of 100,000 women for 9 breast cancer susceptibility genes and a selection of ~100 known susceptibility SNPs. She is one of the PIs for the NIH Big Data to Knowledge Center Translational Genomics, facilitating worldwide standardization of sharing annotated genomics data.

http://cancer.ucsf.edu/people/profiles/vantveer_

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Targeting KRAS stemnessAuthors*: Frank McCormick

Pres #: Section: Presentation Date/Time: Monday, April 18: 10:40-11:05AM

Location: New Orleans Theater A Presentation Type: Major Symposium

__________________________________________________________________________

Translating genomic discoveries into therapy for acute lymphoblastic leukemiaAuthors*: Mignon L. Loh

Pres #: Section: Presentation Date/Time: Monday, April 18: 11:30-11:55AM

Location: Room 260 Presentation Type: Recent Advances in Diagnostics and Therapeutics Research

21

Presentations


Systematic search for synthetic lethal susceptibilities with CRISPRi and CRIPSRaAuthors*: Jonathan Weissman

Pres #: Section: Presentation Date/Time: Monday, April 18: 11:40AM-12:05PM

Location: New Orleans Theater B Presentation Type: Major Symposium

__________________________________________________________________________

Direct drug targeting of K-RasAuthors*: Kevan M. Shokat

Abstract #: Section: Presentation Date/Time: Monday, April 18: 11:40 AM-12:05 PM

Location: New Orleans Theater A Presentation Type: Major Symposium Shokat Lab Expertise: My lab focuses on discovery of new chemical tools to decipher cellular signaling networks, particularly protein kinases and GTPases. Analysis of signal transduction pathways is challenging using traditional tools. Biochemical approaches have limited utility since signaling networks span from the cell surface to the nucleus, confounding reconstitution efforts. Genetic approaches allow specific perturbations, yet can be confounded by the emergent properties of signaling cascades. Chemical and pharmacological approaches enable rapid, reversible & graded inactivation of single components, but highly selective chemical probes are difficult to develop. My lab has solved this problem for protein kinases with a strategy based on a combination of protein engineering and organic synthesis.

http://shokatlab.ucsf.edu/

__________________________________________________________________________

Translation makes an impact: Tailor-made protein expression for metabolism, cancer, and disease Authors*: Davide Ruggero

Abstract #: Section: Presentation Date/Time: Tuesday, April 19: 11:40 AM-12:05 PM

Location: Room 265 Presentation Type: Major Symposium

__________________________________________________________________________

Oncogenic EGFR signaling inhibits the Spred1-NF1 interaction to sustain constitutive Ras signaling Authors*: Evan Markegard, Ellen L. Mercado, Jacqueline Galeas, Marena I. Trinidad, Anatoly Urisman, Frank McCormick

Abstract #: 1874 Section: 4 Presentation Date/Time: Monday, April 19: 1:00-5:00 PM


22

Presentations


MicroRNA-383 located in frequently deleted chromosomal locus 8p22 regulates prostate cancer stem cell marker CD44 Authors*: Nathan Bucay, Kiran Sekhon, Varahram Shahryari, Yozo Mitsui, Guoren Deng, Z. Laura Tabatabai, Shahana Majid, Soichiro Yamamura, Rajvir Dahiya, Yuichiro Tanaka, Sharanjot Saini

Pres #: 1934 Section: 6 Presentation Date/Time: Monday, April 18: 1:00-5:00PM


Saini Lab Expertise: The Saini lab focuses primarily on understanding the molecular basis of progression and metastasis of prostate cancer, in particular the role of microRNA (miRNA) genes located at frequently deleted genomic regions in prostate cancer epithelial-to mesenchymal transition (EMT), recurrence and metastasis. A role for miRNAs that affects EMT and progression and metastasis of human cancers has begun to emerge and Dr. Saini’s research provided initial evidence that miR-203 regulates EMT by directly targeting ZEB2 and other EMT regulators that in turn regulate PCa invasion and metastasis. Her recent research has identified additional novel miRNAs in prostate cancer that play an important role in prostate cancer EMT, recurrence and metastasis.

https://www.ncire.org/research/researchers_by_name/Sharanjot-Saini-PhD/

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A discovery study to identify clinical and genetic risk factors for bevacizumab (BEV)-related gastrointestinal (GI) hemorrhage (HEM) in metastatic castration-resistant prostate cancer (mCRPC) patients (pts) treated on CALGB 90401 (Alliance) Authors*: Jai N. Patel, Chen Jiang, Kouros Owzar, Daniel L. Hertz, Flora A. Mulkey, William K. Kelly, Susan Halabi, Yoichi Furukawa, Cameron Lassiter, Susan G. Dorsey, Paula N. Friedman, Eric J. Small, Michael A. Carducci, John F. Mahoney, Michael J. Kelley, Yusuke Nakamura, Michiaki Kubo, Mark J. Ratain, Michael J. Morris, Howard L. McLeod


Location: Presentation Type: Poster Session Small Lab Expertise: The Stand Up To Cancer Dream Team led by Dr. Eric Small is exploring the idea that resistance to hormonal therapy occurs as a result of the prostate cancer cells using common cellular responses — what the Dream Team calls “adaptive pathways” — to escape the current prostate cancer therapies. They believe that, by identifying these pathways and inhibiting them, they will be able to overcome treatment resistance and profoundly improve the care of men affected by this fatal disease. This team is a six institution consortium to include UC Los Angeles, UC Davis, UC Santa Cruz, University of British Columbia, Oregon Health and Science University, with UCSF as the lead administrative site.

http://cancer.ucsf.edu/people/profiles/small_eric.3671

23

Presentations


Toxicity, bioavailability, pharmacokinetics, tissue distribution and metabolism of a novel small molecule inhibitor of IL-6-induced STAT3 activationAuthors*: Brian F. Kiesel, Robert A. Parise, Jianxia Guo, Donna M. Huryn, Paul A. Johnston, Rafaelle Colombo, Malabika Sen, Jennifer Grandis, Julie L. Eiseman, Jan H. Beumer


Location: Presentation Type: Poster Session Grandis Lab Expertise: We performed a high content screening (HCS) campaign of a 95,000 compound subset of the NIH Molecular Library Screening Center Network (MLSCN) small-molecule library and identified four chemical hit series that selectively inhibited IL-6-induced STAT3 pathway activation in head and neck cancer cell lines that progressed into lead optimization. In the present study we assessed the toxicity, bioavailability, PK , tissue distribution and metabolism of a lead compound (UPCDC10205). Preliminary results indicate that UPCDC10205 was metabolically stable. No gross toxicity was observed in mice administered the maximum soluble dose. UPCDC10205 was widely distributed into tissues and cleared rapidly. Bioavailability was ~5%. In vivo metabolism of UPCDC10205 was by direct glucuronidation, explaining why microsomal stability (reflective of phase I metabolism) did not translate to in vivo metabolic stability.


__________________________________________________________________________

Aurora kinase A (AURKA) dependence underlies the emergence of acquired resistance to 3rd generation EGFR inhibitors in NSCLCAuthors*: Khyati Niral Shah, Henry J. Haringsma, Andrew D. Simmons, Sourav Bandyopadhyay


Location: Presentation Type: Poster Session Bandyopadyay Lab Expertise: In the context of cancer, we are mapping genetic interactions systematically in high-throughput using RNAi and small-molecule based screens. Our primary interest is uncovering genes and pathways which modify the activity of major oncogenes including EGFR and KRAS. Our systems-biology approaches can be used to identify alternative, synthetic lethal targets as well as potential routes of resistance to therapies. In previous work we have interrogated the MYC oncogene in triple negative breast cancer and identified new therapies that can be used in a synthetic lethal manner to target MYC-high breast tumors [Martins et al Cancer Discovery 5(2):154-67 2015]

http://cancersignaling.net/

24

Presentations


Overcoming mTOR resistance mutations with a new generation mTOR inhibitorAuthors*: Vanessa S. Rodrik-Outmezguine, Masanori Okaniwa, Zhan Yao, Chris Novotny, Claire McWhirter, Arpitha Banaji, Helen Won, Wai Wong, Mike Berger, Elisa de Stanchina, Derek G. Barrae, Sabina Cosulich, Teresa Klinowska, Neal Rosen, Kevan M. Shokat


Location: Presentation Type: Poster Session Shokat Lab Expertise: My lab focuses on discovery of new chemical tools to decipher cellular signaling networks, particularly protein kinases and GTPases. Analysis of signal transduction pathways is challenging using traditional tools. Biochemical approaches have limited utility since signaling networks span from the cell surface to the nucleus, confounding reconstitution efforts. Genetic approaches allow specific perturbations, yet can be confounded by the emergent properties of signaling cascades. Chemical and pharmacological approaches enable rapid, reversible & graded inactivation of single components, but highly selective chemical probes are difficult to develop. My lab has solved this problem for protein kinases with a strategy based on a combination of protein engineering and organic synthesis.


__________________________________________________________________________

Functional characterization of combining epigenetic modifiers azacitidine and AG-221 in the TF-1:IDH2R140Q AML modelAuthors*: Vivek S. Chopra, Brian Avanzino, Konstantinos Mavrommatis, Adam Olshen, Jorge DiMartino, Kyle J. MacBeth


Location: Presentation Type: Poster Session Olshen Lab Expertise: My research is focused on developing statistical tools that enhance understanding of genomic data. Tools that I have helped to develop are Circular Binary Segmentation (CBS) for analyzing copy number data, iCluster for integrating multiple types of genomic data, and Babel for identifying genes with unusual levels of translation from ribosome profiling data. I have additional projects in machine learning and analysis of genomic data sets with few replicates. I lead a team of computational biologists as Director of the Computational Biology Core in the Helen Diller Family Comprehensive Cancer Center.

http://cancer.ucsf.edu/people/profiles/olshen_adam.3576

25

Presentations


The genetic evolution of melanomaAuthors*: Alan H. Shain, Richard Yu, Iwei Yeh, Jamal Benhamida, Ivanka Kovalyshyn, Aravindhan Sriharan, Eric Talevich, Reinhard Dummer, Jeffrey North, Laura Pincus, Beth Ruben, William Rickaby, Corrado D’Arrigo, Alistair Robson, Robert Judson, Nancy Joseph, Boris Bastian


Location: Presentation Type: Poster Session Bastian Lab Expertise: My laboratory is interested in the genetic alterations involved in skin cancer pathogenesis and predisposition as well as in understanding their role in biology, markers to improve diagnosis, and targets for treatment.

__________________________________________________________________________

Combined BET-bromodomain and CDK2 inhibition in MYC-driven medulloblastomaAuthors*: Sara Bolin, Anna Borgenvik, Camilla Persson, Gabriela Rosén, Anders Sundström, Jun Qi, James E. Bradner, William A. Weiss, Yoon-Jae Cho, Holger Weishaupt, Fredrik J. Swartling


Location: Presentation Type: Poster Session Weiss Lab Expertise: The Weiss lab is broadly interested in developing and characterizing mouse models that faithfully recapitulate the biology and genetics of human tumors of the nervous system, and using observations in the mouse to inform the biology, genetics, and therapy of human tumors.

Specifically, we are: 1) Identifying the subsequent genetic events that promote tumorigenesis.2) Studying cancer stem and progenitor cells to understand their contribution to malignant progression. 3) Evaluating new targets, therapies, and mechanistic rationales for combining targeted agents.

http://waweisslab.ucsf.edu/

__________________________________________________________________________

Optimizing cervical cancer screening for HIV-infected women: A risk-based approachAuthors*: Hilary A. Robbins, L. Stewart Massad, Christopher B. Pierce, Lisa Flowers, Teresa M. Darragh, Howard Minkoff, Lisa Rahangdale, Marla J. Keller, Joel Milam, Margaret Fisch, Sadeep Shrestha, Christine Colie, Howard Strickler, Gypsyamber D’Souza



26

Presentations


Association of mammographic density measures and breast cancer ‘intrinsic’ molecular subtypesAuthors*: Aaron D. Norman, Rulla M. Tamimi, Christopher G. Scoe, Kimberly A. Bertrand, Matthew R. Jensen, Daniel W. Visscher, Fergus J. Couch, John Shepherd, Bo Fan, Yunn-Yi Chen, Lin Ma, Andrew Beck, Vernon S. Pankratz, Karla Kerlikowske, Celine M. Vachon


Location: Presentation Type: Poster Session Kerlikowski Lab Expertise: My lab focuses on breast imaging and the epidemiology of invasive breast cancer, DCIS and breast density, and risk prediction models for invasive breast cancer. We have developed cohorts of women at risk for invasive breast cancer and DCIS and developed comprehensive databases that include breast imaging, pathologic, clinical, biomarker, and risk factor data, as well as follow-up for subsequent disease and death.

http://cancer.ucsf.edu/people/profiles/kerlikowske_karla.3457

__________________________________________________________________________

Common genetic variants associated with breast cancer risk used in the Athena study to enhance models identifying women for breast cancer chemopreventionAuthors*: Sarah Theiner, Sarah D. Sawyer, Paige Kendall, Alexandra S. Perry, Denise Wolf, Scott Huntsman, Bo Pan, Jeffery A. Tice, David A. Pearce, Thomas Cink, Laura Esserman, Elad Ziv, Laura van ‘t Veer


Location: Presentation Type: Poster Session van ‘t Veer Lab Expertise: Dr. van ’t Veer’s research focuses on personalized medicine & advancing patient management based on knowledge of the genetic makeup of the tumor as well as the genetic makeup of the patient. Her laboratory investigates human kinases & how kinase inhibitors elicit response & resistance, which is also utilized to understand agent efficacy in the I-SPY 2 TRIAL. She is the PI of the Athena Breast Health Network, a 150,000 women cohort study evaluating new paradigms to enhance breast health. She leads the targeted genome testing of 100,000 women for 9 breast cancer susceptibility genes and a selection of ~100 known susceptibility SNPs. She is one of the PIs for the NIH Big Data to Knowledge Center Translational Genomics, facilitating worldwide standardization of sharing annotated genomics data.


27

Presentations


A stem cell program in metastatic human breast cancerAuthors*: Zena Werb

Pres #: Section: Presentation Date/Time: Monday, April 18: 1:10-1:35PM

Location: New Orleans Theater C Presentation Type: Major Symposium

__________________________________________________________________________

Molecular evolution and taxonomy of melanomaAuthors*: Boris C. Bastien


Location: Room 391 Presentation Type: Recent Advances in Organ Site Research Bastian Lab Expertise: My laboratory is interested in the genetic alterations involved in skin cancer pathogenesis and predisposition as well as in understanding their role in biology, markers to improve

diagnosis, and targets for treatment.

__________________________________________________________________________

Molecular mechanisms of driver mutations in gliomaAuthors*: Joseph F. Costello


Location: Room 354 Presentation Type: Recent Advances in Organ Site Research

Costello Lab Expertise (Limit 800 characters): Our goal is to understand the full life history of human tumors,

from the first mutation and epimutation through clonal selection and tumor recurrence. We use NGS to

discover patterns and interdependencies of genetic mutations, epigenetic alterations and gene expression

changes. Current projects incorporate MRI guided tumor biopsies and treatment data with longitudinal

genomics to allow the reconstruction of tumor evolution in the context of the human tumor in vivo. We recently

discovered the mechanism by which mutations in the TERT gene promoter leads to telomerase activation.

https://costellolab.ucsf.edu/

28

Presentations


Off-target resistance to inhibitors of BCR-ABL and FLT3 in myeloid malignanciesAuthors*: Neil P. Shah


Location: Room 265 Presentation Type: Recent Advances in Organ Site Research Shah Lab Expertise : The Shah lab is interested in advancing targeted therapeutics for hematologic malignancies through basic studies of in vitro and in vivo model systems to gain a better understanding critical vulnerabilities of malignant cells, and through translational/clinical studies of samples obtained from patients participating in early phase monotherapy clinical studies to identify, validate and override mechanisms of resistance to these agents.

https://shah.ucsf.edu/

__________________________________________________________________________

Translation of hyperpolarized 13C imaging to the clinicAuthors*: John Kurhanewicz


Location: Room 260 Presentation Type: Major Symposium

Kurhanewicz Lab Expertise

__________________________________________________________________________

Targeting adaptive pathways in metastatic treatment resistantprostate cancerAuthors*: Eric Small


Location: Room 243 Presentation Type: Special Session Small Lab Expertise: The Stand Up To Cancer Dream Team led by Dr. Eric Small is exploring the idea that resistance to hormonal therapy occurs as a result of the prostate cancer cells using common cellular responses — what the Dream Team calls “adaptive pathways” — to escape the current prostate cancer therapies. They believe that, by identifying these pathways and inhibiting them, they will be able to overcome treatment resistance and profoundly improve the care of men affected by this fatal disease. This team is a six institution consortium to include UC Los Angeles, UC Davis, UC Santa Cruz, University of British Columbia, Oregon Health and Science University, with UCSF as the lead administrative site.

http://cancer.ucsf.edu/people/profiles/small_eric.3671

29

Presentations


Inhibition of fatty-acid oxidation as a therapy for MYC-overexpressing triple-negative breast cancerAuthors*: Roman Camarda, Alicia Y. Zhou, Rebecca A. Kohnz, Sanjeev Balakrishnan, Celine Mahieu, Brieany Anderton, Henok Eyob, Shingo Kajimura, Aaron Tward, Gregor Krings, Daniel K. Nomura, Andrei Goga

Pres #: 2673 Section: Presentation Date/Time: Monday, April 18: 4:05-4:20PM

Location: Room 265 Presentation Type: Minisymposium Goga Lab Expertise: Tumor cells are driven to proliferate, alter their metabolism, and deregulate cell death pathways by oncogene over-expression or the loss of tumor-suppressor genes. We seek to understand how oncogenes alter these pathways using cell-based and transgenic animal models. We are especially interested in how the prototypical oncogene Myc acts in diverse tumor types, including amongst the most aggressive breast and liver cancers and lymphomas. Myc has also been postulated to drive a ‘stem cell like’ gene expression pattern which may regulate tumor stem cell function. We seek to elucidate the genes and pathways that are indispensable for Myc function, and thus uncover potential ‘achilles heels’ of tumor cells. Our ultimate goal is to translate our basic discoveries to novel cancer therapeutics.

http://oncogenes.net/Goga_Lab/Home.html

__________________________________________________________________________

GAPVAC-101 phase I trial: First data of an innovative actively personalized peptide vaccination trial in patients with newly diagnosed glioblastomaAuthors*: Norbert Hilf, Katrin Frenzel, Sabrina Kueruff-Coqui, Sandra Heesch, Sebastian Kreiter, Arie Admon, Valesca Bukur, Sjoerd van der Burg, Cecile Goueefangeas, Judith R. Kroep, Marij Schoenmaekers-Welters, Jordi Piro, Berta Ponsati, Hans Skovgaard Poulsen, Ulrik Lassen, Francisco Martinez-Ricarte, Jordi Rodon, Juan Sahuquillo, Monika Stieglbauer, Stefan Stevanovic, Per thor Straten, Marco Skardelly, Ghazaleh Tabatabai, Michael Plaeen, David Capper, Andreas von Deimling, Valérie Dutoit, Hideho Okada, Christian Oeensmeier, Randi Kristina Feist, Jens Fritsche, Karoline Laske, Peter Lewandrowski, Martin Löwer, Regina Mendryzk, Miriam Meyer, Carsten Reinhardt, Bernhard Rössler, Anna Paruzynski, Nina Pawlowski, Coleee Song, Stevermann Lea, Toni Weinschenk, Christoph Huber, Hans-Georg Rammensee, Pierre-Yves Dietrich, Wick Wolfgang, Ugur Sahin, Harpreet Singh-Jasuja

Pres #: 2654 Section: Presentation Date/Time: Monday, April 18: 4:35-4:50PM

Location: New Orleans Theater B Presentation Type: Minisymposium Okada Lab Expertise: As a translational physician scientist, Dr. Okada and his lab are focused on development of novel immunotherapeutic strategies for brain tumor patients. For example, Dr. Okada conducted one of the first immune gene therapy trials in patients with malignant glioma. His lab was also the first to identify and fully characterized cytotoxic T-lymphocyte epitopes for gliomas. Dr. Okada has also delineated the role of an integrin receptor very late activation antigen-4 and chemokine CXCL10 in efficient trafficking of T-cells to brain tumor sites. Dr. Okada has integrated these findings to develop a number of vaccine trials in both adult and pediatric glioma patients. More recently, his group developed a novel chimeric antigen receptor targeting glioblastoma cells, and are currently conducting a pilot trial.


30

Presentations


Sensitizing the hypoxic tumor microenvironment with OMX, a breakthrough oxygen delivery protein: From protein engineering to clinical trialAuthors*: Ana Krtolica, Natacha Le Moan, Philberta Leung, Youngho Seo, Jonathan Winger, Henry Van Brocklin, Michael Kent, Stephen Cary

Pres #: 2790 Section: 5 Presentation Date/Time: Tuesday, April 19: 8:00AM-12:00PM

Location: Presentation Type: Poster Session Van Brocklin Lab Expertise: The VanBrocklin laboratory focuses on developing nuclear imaging agents targeting cell surface proteins (receptors, enzymes and transporters) and signalling pathways and mechanisms by PET and SPECT imaging. We have developed imaging agents covering a broad range of molecular motifs from small molecules, antibodies, antibody fragments (e.g., Fabs, scFv, and diabodies), and aptamers, to proteins and peptides. We synthesize, evaluate and validate tracer mechanisms of localization and retention at the target site. We utilize in vitro and in vivo model systems to test the probes and interpret the data collected from these systems to determine their utility for research or as a future diagnostic. We have successfully translated many of these tracers into humans for drug development or evaluation as future diagnostics.

http://cancer.ucsf.edu/people/profiles/vanbrocklin_henry.3696

__________________________________________________________________________

TPX2 overexpression is essential for the survival of MYC-driven triple negative breast cancerAuthors*: Julia Rohrberg, Alexandra Corella, Sanjeev Balakrishnan, Andrei Goga



Goga Lab Expertise: Tumor cells are driven to proliferate, alter their metabolism, and deregulate cell death pathways by oncogene over-expression or the loss of tumor-suppressor genes. We seek to understand how oncogenes alter these pathways using cell-based and transgenic animal models. We are especially interested in how the prototypical oncogene Myc acts in diverse tumor types, including amongst the most aggressive breast and liver cancers and lymphomas. Myc has also been postulated to drive a ‘stem cell like’ gene expression pattern which may regulate tumor stem cell function. We seek to elucidate the genes and pathways that are indispensable for Myc function, and thus uncover potential ‘achilles heels’ of tumor cells. Our ultimate goal is to translate our basic discoveries to novel cancer therapeutics.

http://oncogenes.net/Goga_Lab/Home.html

31

Presentations


Genetic prediction of VEGF-A plasma levels in cancer patientsAuthors*: Federico Innocenti, Chen Jiang, Alexander Sibley, Amy Etheridge, Yoichi Furukawa, Michiaki Kubo, Hedy L. Kindler, Alan P. Venook, Herber I. Hurwitz, Andrew B. Nixon, Kouros Owzar



__________________________________________________________________________

Longitudinal changes in volumetric breast density with adjuvant endocrine therapy among women with breast cancerAuthors*: Natalie J. Engmann, Celine M. Vachon, Christopher G. Scoe, Maehew R. Jensen, Lin Ma, Kathleen R. Brandt, Amir P. Mahmoudzadeh, Serghei Malkov, Dana H. Whaley, Carrie B. Hruska, Fang F. Wu, Stacey J. Winham, Diana L. Miglioretti, Aaron D. Norman, John J. Heine, John Shepherd, V. Shane Pankratz, Karla Kerlikowske



Kerlikowske Lab Expertise: My lab focuses on breast imaging and the epidemiology of invasive breast cancer, DCIS and breast density, and risk prediction models for invasive breast cancer. We have developed cohorts of women at risk for invasive breast cancer and DCIS and developed comprehensive databases that include breast imaging, pathologic, clinical, biomarker, and risk factor data, as well as follow-up for subsequent disease and death.

http://cancer.ucsf.edu/people/profiles/kerlikowske_karla.3457

__________________________________________________________________________

Antiangiogenic therapy and immune modulationAuthors*: Gabriele Bergers

Pres #: Section: Presentation Date/Time: Tuesday, April 19: 10:40-11:05AM

Location: Room 293 Presentation Type: Major Symposium Bergers Lab Expertise: The Bergers laboratory focuses on revealing the dialogue between the tumor cell compartment and the vascular niche, of which the vasculature is an integral component. The vascular niche consists of distinct cell types and specialized matrices that provide signals controlling stem cell proliferation, fate specification, and protection in not only normal tissue, but tumors, as well. The long-term goal of Dr. Bergers’ research is to conduct a comprehensive investigation that defines the heterotypical signals of the tumor-host dialogue in the vascular niche in regulating neovascularization, stem cell maintenance, and tumor invasion during tumor progression and therapeutic resistance.


32

Presentations


Novel genetic variants protective against breast cancer in LatinasAuthors*: Laura Fejerman

Pres #: Section: Presentation Date/Time: Tuesday, April 19: 11:00-11:20AM

Location: Room 383 Presentation Type: Major Symposium Fejerman Lab Expertise: Dr. Fejerman focuses on the discovery of genetic and non-genetic factors that contribute to breast cancer risk and prognosis in Latinas. Her past work established a relationship between genetic ancestry and breast cancer risk, where higher European ancestry in U.S. and Mexican Latinas was associated with an increased risk. Her subsequent research has built upon this observation, exploring genetic variants, through admixture mapping and genome-wide association approaches, as well as the possible environmental and lifestyle related factors, and ancestry-gene interactions. Recent work explores disparities in breast cancer prognosis by genetic ancestry in Latinas and its potential causes.

http://fejerman.ucsf.edu

__________________________________________________________________________

A new innovative and robust targeted deep sequencing system: 36 hours turn round time from patient samples to the final mutation reportAuthors*: Pedro Mendez, Jun-Hee Yoon, Sharon Lee, James Kim, Jenny Dang, Thomas Kim, David Jablons, Il Jin Kim

Pres #: 3609 Section: 6 Presentation Date/Time: Tuesday, April 19: 1:00-5:00PM

Location: P resentation Type: Poster Session Kim Lab Expertise: Dr. Il-Jin Kim has focused his career on three important cancer-related areas: 1) cancer genetics and genomics, 2) early detection and 3) cancer prevention. Dr. Kim has published approximately 70 papers in these areas. He has also been granted three patents for mutation detection methods. Projects included in these areas include: genetic screening in hereditary (familial) cancers to distinguishing carriers from non-carriers, development of new genetic screening methods for cancer prevention, and genome-wide gene expression microarray analysis.

Current projects in the Kim Lab include: Cancer Genetics and Genomics, Early Detection, Cancer Prevention.

http://kimlab.surgery.ucsf.edu/about-us.aspx

33

Presentations


Overcoming resistance to HER2 inhibitors through cell based screeningAuthors*: Chris J. Novotny, Sirkku Pollari, Jin H. Park, Mark A. Lemmon, Peter G. Schultz, Weijun Shen, Kevan M. Shokat


Location: Presentation Type: Poster Session Shokat Lab Expertise: My lab focuses on discovery of new chemical tools to decipher cellular signaling networks, particularly protein kinases and GTPases. Analysis of signal transduction pathways is challenging using traditional tools. Biochemical approaches have limited utility since signaling networks span from the cell surface to the nucleus, confounding reconstitution efforts. Genetic approaches allow specific perturbations, yet can be confounded by the emergent properties of signaling cascades. Chemical and pharmacological approaches enable rapid, reversible & graded inactivation of single components, but highly selective chemical probes are difficult to develop. My lab has solved this problem for protein kinases with a strategy based on a combination of protein engineering and organic synthesis.


__________________________________________________________________________

Highly sensitive detection of MYB-NFIB fusion transcripts in adenoid cystic carcinomaAuthors*: Piotr T. Wysocki, Shizhang Ling, Chunbo Shao, Marieea Tan, David Sidransky, Patrick Ha, Mariana Brait



Ha Lab Expertise: Dr. Ha’s lab interests align with his clinical practice of managing patients with complex head and neck cancers. He has had multiple NIH grants examining the molecular underpinnings of salivary gland adenoid cystic carcinoma in order to learn more about this rare but deadly disease. He serves on the editorial board of several journals including Head and Neck and Oral Oncology, and is now serving as the Chief of Head and Neck Surgical Oncology at the University of California San Francisco.

http://ohns.ucsf.edu/patrick-ha

__________________________________________________________________________

Structural basis of recognition of farnesylated and methylated KRAS4b by PDE-δAuthors*: Sathiya Dharmaiah, Lakshman Bindu, Peter Frank, William Gilleee, Dominic Esposito, Dwight Nissley, Frank McCormick, Andrew Stephen, Dhirendra Simanshu

Pres #: 4373 Section: Presentation Date/Time: Tuesday, April 19: 3:05-3:20PM

Location: Room 354 Presentation Type: Minisymposium

34

Presentations


T cell repertoire diversification is associated with immune related toxicities following immune checkpoint inhibition in metastatic cancer patientsAuthors*: David Y. Oh, Jason Cham, Li Zhang, Grant Fong, Mark Klinger, Malek Faham, Lawrence Fong

Pres #: 4362 Section: Presentation Date/Time: Tuesday, April 19: 3:50-4:05PM

Location: New Orleans Theater C Presentation Type: Minisymposium

Fong Lab Expertise: My lab focuses on how the immune system interacts with cancer as well as exploring tumor immunotherapies in mouse models and in patients. Our primary focus is in immunotherapy of GI and GU malignancies. We investigate how immunotherapies such as immune checkpoint inhibitors and cancer vaccines can enhance anti-tumor immunity both systemically and in the tumor microenvironment. Performing neoadjuvant immunotherapy trials, we determine how specific therapies can recruit immune effectors in cancer patients. Moreover, we have studied how clinical responders may differ from clinical non-responders. We are applying unbiased approaches to studying antigen-specific responses that are modulated in these patients and are currently developing biomarkers that may be predictive of clinical efficacy.

http://hemonc.ucsf.edu/fonglab/

__________________________________________________________________________

Mechanism of PI3K activation by the HER3/ErbB3 receptor

Authors*: Nicole Michael, Michael Hopkins, Natalia Jura

Pres #: 4590 Section: 8 Presentation Date/Time: Wednesday, April 20: 8:00AM-12:00PM

Location: Presentation Type: Poster Session Jura Lab Expertise: The main interest of our laboratory is to understand molecular principles of signal transduction events. We investigate them at the level of enzymatic function and molecular structure of signaling proteins. Our current focus is on understanding how membrane-associated kinases, such as receptor tyrosine kinases, assemble into functional complexes and interface with the plasma membrane. We also investigate alternative non-catalytic roles of kinase scaffolds and seek to identify small molecule inhibitors that target these poorly understood kinase functions in human diseases.

http://www.cvri.ucsf.edu/~jura/lab/Jura_Lab_Home.html

35

Presentations


Direct analysis of tumor immune infiltrates for “Exhausted” CD8+ T-Cells and BDCA3+ predicts responses in melanomaAuthors*: Kimberly Loo, Katy K. Tsai, Adi Nosrati, Mariela Pauli, Robert Sanchez, Miranda Broz, Lorenzo Nardo, Miguel Pampaloni, Michael Alvarado, Paul Tumeh, Alain Algazi, Michael Rosenblum, Matthew Krummel, Adil Daud


Location: Presentation Type: Poster Session Daud Lab Expertise: Our group at UCSF is focused on developing new immunotherapy agents and specifically understanding the biology of the immune response to PD-1 in melanoma. We developed IL-12 gene therapy in melanoma and carried out the first in human clinical trial in 2005-2007. Based on this work, IL-12 electroporation is being explored in many cancers as an immune agent and as a combination treatment with PD-1 and other checkpoint inhibitors in melanoma. I have been involved in the development of anti-PD-1 antibodies for melanoma. With my colleagues Michael Rosenblum and Max Krummel at UCSF, we have developed a novel assay that profiles the intra-tumoral microenvironment in depth and can predict non-response to PD-1. We are currently exploring novel strategies for PD-1 non-responsive subsets of melanoma (and potentially other cancers).

http://cancer.ucsf.edu/people/profiles/daud_adil.3622

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Interplay between ECM stiffness, miR-203 and mammographic densityAuthors*: Ivory Dean, Irene Acerbi, Alfred Au, Yunn-Yi Chen, Shelley Hwang, Valerie Weaver



Weaver Lab Expertise: The extracellular matrix (ECM), the noncellular component of the microenvironment, influences cell growth, survival, migration and tissue-specific differentiation through a repertoire of cellular receptors including integrins, syndecans and discoidin receptors. We are exploring the molecular mechanisms whereby these ECM receptors modulate cell fate: specifically, how mechanical and topological properties of the matrix, which are related to its composition and organization, regulate the function of matrix receptors to alter cell behavior. Our research program is broadly divided into two fields of inquiry: (1) how matrix composition and organization influences mammary tissue development and tumor progression and (2) to clarify the role of matrix force on embryonic and adult stem cell fate.

http://weaverlab.ucsf.edu

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Presentations


IDH mutation-induced suppression of type-1 anti-glioma immune responsesAuthors*: Gary Kohanbash, Brian Ahn, Shruti Shrivastav, Diego Carrera, Joseph Costello, Hideho Okada



Okada Lab Expertise: As a translational physician scientist, Dr. Okada and his lab are focused on development of novel immunotherapeutic strategies for brain tumor patients. For example, Dr. Okada conducted one of the first immune gene therapy trials in patients with malignant glioma. His lab was also the first to identify and fully characterized cytotoxic T-lymphocyte epitopes for gliomas. Dr. Okada has also delineated the role of an integrin receptor very late activation antigen-4 and chemokine CXCL10 in efficient trafficking of T-cells to brain tumor sites. Dr. Okada has integrated these findings to develop a number of vaccine trials in both adult and pediatric glioma patients. More recently, his group developed a novel chimeric antigen receptor targeting glioblastoma cells, and are currently conducting a pilot trial.


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STAT3 inhibition as chemoprevention in a chemically induced mouse model of HNSCCAuthors*: Noah D. Peyser, Lin Wang, Marie Acquafondata, Maria Freilino, Hua Li, Yan Zeng, Malabika Sen, William E. Gooding, Daniel E. Johnson, Jennifer R. Grandis


Location: Presentation Type: Poster Session Grandis Lab Expertise: We have determined that STAT3 is a plausible therapeutic target in head and neck cancer where STAT3 activation contributes to chemoresistance. Studies to date have focused on the mechanisms of STAT3 hyperactivation in HNSCC as well as developing strategies to block STAT3 signaling in preclinical models and HNSCC patients. Loss of function genetic alterations of protein tyrosine receptor phosphatases contribute to STAT3 activation in HNSCC where STAT3 mutations are rare. We have developed and patented a decoy oligonucleotide strategy to block STAT3, demonstrated pharmacodynamic effiacy in a phase 0 trial and are poised to assess the STAT3 decoy in a phase I study pending completion of IND-directed pharm/tox assessment. Preclinical studies demonstrate antitumor efficacy in combination with cetuximab in HNSCC models and erlotinib in NSCLC.


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Presentations


Caffeic acid phenethyl ester (CAPE) reverses aggressive breast cancer in the radiation chimera model Authors*: Coral O. Omene, Manan Patel, Irineu IllaBochaca, Mary Helen Barcellos-Hoff



Barcellos-Hoff Lab Expertise: Our lab focuses on stromal epithelial interactions during mammary carcinogenesis. We developed a novel radiation chimera mammary model in which the host mouse is irradiated and subsequently transplanted with oncogenically primed mammary epithelia that lack the tumor suppressor, Trp53. Diverse carcinomas, as assessed by markers or intrinsic subtype signatures, arise from this epithelium that recapitulate the spectrum of breast cancer in women. The influence of host biology on the breast cancer spectrum provides a novel perspective on extrinsic drivers of aggressive cancers that recur and metastasize. This diversity also underscores this as a particularly relevant murine model in which to explore therapuetic response of spontaneous cancer in an immunocompetent mouse or, as reported here, to test chemoprevention strategies.

http://cancer.ucsf.edu/people/profiles/barcellos-hoff_mary.6915

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