MolecularOncology - Cambridge University...
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Molecular OncologyCauses of Cancer and Targets for Treatment
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Cambridge University Press978-0-521-87662-9 - Molecular Oncology: Causes of Cancer and Targets for TreatmentEdited by Edward P. Gelmann, Charles L. Sawyers and Frank J. Rauscher IIIFrontmatterMore information
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Cambridge University Press978-0-521-87662-9 - Molecular Oncology: Causes of Cancer and Targets for TreatmentEdited by Edward P. Gelmann, Charles L. Sawyers and Frank J. Rauscher IIIFrontmatterMore information
Molecular OncologyCauses of Cancer and Targets for TreatmentEdited byEdward P. GelmannChief, Division of Hematology/Oncology and Deputy Director for Clinical Research, Herbert Irving Comprehensive Cancer Centerand Columbia University Medical Center, New York, NY, USA
Charles L. SawyersChair, Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York, NY, and Investigator,Howard Hughes Medical Institute, Chevy Chase, MD, USA
Frank J. Rauscher IIIProfessor, Gene Expression and Regulation Program; Professor, Tumor Microenvironment and Metastasis Program;Deputy Director for Basic Research, Wistar Institute Cancer Center, Philadelphia, PA, USA
www.cambridge.org© in this web service Cambridge University Press
Cambridge University Press978-0-521-87662-9 - Molecular Oncology: Causes of Cancer and Targets for TreatmentEdited by Edward P. Gelmann, Charles L. Sawyers and Frank J. Rauscher IIIFrontmatterMore information
University Printing House, Cambridge CB2 8BS, United Kingdom
Published in the United States of America by Cambridge UniversityPress, New York
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It furthers the University’s mission by disseminating knowledge in thepursuit of education, learning and research at the highestinternational levels of excellence.
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First published 2014
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A catalog record for this publication is available from the British Library
Library of Congress Cataloging in Publication dataMolecular oncology : causes of cancer and targets for treatment /edited by Edward P. Gelmann, Chief, Division ofHematology/Oncology and Deputy Director for Clinical Research,Herbert Irving Comprehensive Cancer Center and ColumbiaUniversity Medical Center, New York, NY, USA, Charles L. Sawyers,Chair, Human Oncology and Pathogenesis Program, MemorialSloan-Kettering Cancer Center, New York, NY, USA, Frank J.Rauscher III, Professor, Gene Expression and Regulation Program,Professor, Tumor Microenvironment and Metastasis Program, DeputyDirector for Basic Research, Wistar Institute Cancer Center,Philadelphia, PA, USA.pages cm
Includes bibliographical references and index.ISBN 978-0-521-87662-9 (hardback)1. Cancer – Molecular aspects. 2. Tumor markers.3. Carcinogenesis. I. Gelmann, Edward P., 1953– II. Sawyers,Charles L. III. Rauscher, F. J. (Frank Joseph), 1957–RC268.4.M675 2014616.99′4 – dc23 2013012165
ISBN 978-0-521-87662-9 Hardback
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Cambridge University Press978-0-521-87662-9 - Molecular Oncology: Causes of Cancer and Targets for TreatmentEdited by Edward P. Gelmann, Charles L. Sawyers and Frank J. Rauscher IIIFrontmatterMore information
This book is dedicated to the scientists who made the discoveries,to the members of industry who developed the pharmaceuticals,to the clinicians whose trials turned medicines into therapies,and to the patients whose participation in research isessential and whose diseases we work to relieve.
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Cambridge University Press978-0-521-87662-9 - Molecular Oncology: Causes of Cancer and Targets for TreatmentEdited by Edward P. Gelmann, Charles L. Sawyers and Frank J. Rauscher IIIFrontmatterMore information
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Cambridge University Press978-0-521-87662-9 - Molecular Oncology: Causes of Cancer and Targets for TreatmentEdited by Edward P. Gelmann, Charles L. Sawyers and Frank J. Rauscher IIIFrontmatterMore information
Contents
List of contributors xiPreface xxi
Part 1.1 Analytical techniques: analysis of DNA1. Cancer genome sequencing 1
Abizar Lakdawalla, Jeffrey Fisher, Mostafa Ronaghi, andJian-Bing Fan
2. Genome-wide association studies of cancerpredisposition 10Zsofia K. Stadler, Sohela Shah, and Kenneth Offit
3. Comparative genomic hybridization 21Donna G. Albertson and Daniel Pinkel
4. Chromosome analysis: molecular cytogeneticapproaches 28Thomas Ried
5. DNAmethylation 37Marsha Reyngold and Timothy A. Chan
Part 1.2 Analytical techniques: analysis of RNA6. The application of high-throughput analyses to
cancer diagnosis and prognosis 46Edward P. Gelmann
7. Cancer proteomics 52Samir Hanash and Ayumu Taguchi
8. Tyrosine kinome profiling: oncogenic mutationsand therapeutic targeting in cancer 58Paramita Ghosh, Yun Qiu, Ling-Yu Wang, andHsing-Jien Kung
9. In situ techniques for protein analysis in tumortissue 76Valsamo K. Anagnostou and David L. Rimm
Part 2.1 Molecular pathways underlyingcarcinogenesis: signal transduction
10. HER 85Wolfgang J. Kostler and Yosef Yarden
11. The insulin–insulin-like growth-factor receptorfamily as a therapeutic target in oncology 110Michael Pollak
12. TGF-� signaling in stem cells andtumorigenesis 119Ying Li, Ruth He, and Lopa Mishra
13. Platelet-derived growth factor 135Arne Ostman and Carl-Henrik Heldin
14. FMS-related tyrosine kinase 3 144Soheil Meshinchi and Derek L. Stirewalt
15. ALK: Anaplastic lymphoma kinase 162Karen Pulford
16. The FGF signaling axis in prostatetumorigenesis 190Fen Wang, Yongde Luo, and Wallace L. McKeehan
17. Hepatocyte growth factor/Met signalingin cancer 204Fabiola Cecchi, Young H. Lee, and Donald P. Bottaro
18. PI3K 218Kevin D. Courtney and Lewis C. Cantley
19. Intra-cellular tyrosine kinase 231Rosalyn B. Irby and Timothy J. Yeatman
20. WNT signaling in neoplasia 243Masaru Katoh
21. Ras 258Adrienne D. Cox and Molly J. DeCristo
22. BRAFmutations in human cancer: biologic andtherapeutic implications 272Moriah H. Nissan and David B. Solit
23. Aurora kinases in cancer: an opportunity fortargeted therapy 278Vikas Sehdev, Altaf A. Dar, and Wael El-Rifai
24. 14-3-3 proteins in cancer 293Alexandra K. Gardino and Michael B. Yaffe
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Contents
25. STAT signaling as amolecular target for cancertherapy 305Hua Yu and Richard Jove
26. TheMYC oncogene family in humancancer 313Michael D. Cole
27. Jun proteins and AP-1 in tumorigenesis 319Shira Anzi and Eitan Shaulian
28. Forkhead box proteins: the tuningforks in cancer development andtreatment 328Eric W.-F. Lam, Kyle W. Muir, andChuay-Yeng Koo
29. NF-�B and cancer 336Willscott E. Naugler and Michael Karin
Part 2.2 Molecular pathways underlyingcarcinogenesis: apoptosis
30. Apoptosis: the extrinsic pathway 353Xinchen Teng and J. Marie Hardwick
31. Apoptosis: the intrinsic pathway 367Jody White
Part 2.3 Molecular pathways underlyingcarcinogenesis: nuclear receptors
32. Androgens and the androgen receptor (AR) 378Nicole L. Moore, Margaret M. Centenera,Lisa M. Butler, Theresa E. Hickey, andWayne D. Tilley
33. Emerging roles of peroxisomeproliferator-activated receptor gammain cancer 392Chenguang Wang, Xuemin Zhang, Lifeng Tian, andRichard G. Pestell
Part 2.4 Molecular pathways underlyingcarcinogenesis: DNA repair
34. The ATM-mediated DNA-damage response 403Yosef Shiloh
35. Werner syndrome: association of premature agingand cancer predisposition 423Byungchan Ahn, Tinna Stevnsner, and Vilhelm A. Bohr
36. Hereditary disorders of DNA repair and DNAdamage tolerance that predispose to neoplastictransformation 434Errol C. Friedberg and Roger A. Schultz
37. Telomerase: target for cancer treatment 442Jerry W. Shay and Woodring E. Wright
Part 2.5 Molecular pathways underlyingcarcinogenesis: cell cycle
38. Cell cycle: mechanisms of control and dysregulationin cancer 452Erik S. Knudsen, Ryan J. Bourgo, Elizabeth L. Gosnell,Jeffry L. Dean, and A. Kathleen McClendon
39. DNA-damage-induced apoptosis 465Shun J. Lee, Benjamin F. O’Connor, Scott A. Stuart, andJean Y. J. Wang
Part 2.6 Molecular pathways underlyingcarcinogenesis: other pathways
40. The ubiquitin/proteasome pathway inneoplasia 473Robert C. A. M. van Waardenburg andMary-Ann Bjornsti
41. Small silencing non-coding RNAs: cancerconnections and significance 481Milena S. Nicoloso and George A. Calin
Part 3.1 Molecular pathology: carcinomas42. Head and neck cancer 497
Kelly Quesnelle, Jennifer Grandis, Karl Munger, andMarshall R. Posner
43. Lung cancer 506Jill E. Larsen and John D. Minna
44. Esophageal cancer 526DuyKhanh P. Ceppa andThomas A. D’Amico
45. Gastric cancer 532Yoshiaki Ito and Khay Guan Yeoh
46. Small-bowel tumors: molecular mechanisms andtargeted therapy 542Allan D. Spigelman and Janindra Warusavitarne
47. Colon and rectal cancer 547Erin M. Perchiniak and Joanna Groden
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Cambridge University Press978-0-521-87662-9 - Molecular Oncology: Causes of Cancer and Targets for TreatmentEdited by Edward P. Gelmann, Charles L. Sawyers and Frank J. Rauscher IIIFrontmatterMore information
Contents
48. Pancreatic cancer 557Siong-Seng Liau and David A. Tuveson
49. Hepatocellular carcinoma 569Augusto Villanueva, Yujin Hoshida, Derek Y. Chiang,and Josep M. Llovet
50. Renal-cell carcinomas 579Kyle A. Furge and Bin T. Teh
51. Bladder cancer 584Robert S. Svatek and Colin P. Dinney
52. Prostate cancer 591Kaustubh Datta and Donald J. Tindall
53. Targeted therapies in breast cancer 598Nancy E. Hynes and Gwen MacDonald
54. Molecular targets for epithelial ovarian cancer 606Grace K. Suh, Bryan T. Hennessy, Roeland Verhaak,Ji-Yeon Yang, Gordon B. Mills, and Robert C. Bast, Jr.
55. Testicular cancer: germ-cell tumors (GCTs) 619J. Wolter Oosterhuis and Leendert H. J. Looijenga
56. Cervical cancer 630John Doorbar
Part 3.2 Molecular pathology: cancers of thenervous system
57. Brain tumors 641Chang-Hyuk Kwon, Dennis K. Burns, and Luis F. Parada
58. Mechanisms of pituitary tumorigenesis 652Shereen Ezzat and Sylvia L. Asa
59. Molecular oncology of neuroblastoma 669Vandana Batra, Rebecca J. Deyell, and John M. Maris
60. Neurofibromatosis type I 679Rachel S. Darken and David H. Gutmann
Part 3.3 Molecular pathology: cancersof the skin
61. Squamous-cell carcinoma 686Carter Van Waes, Yansong Bian, Clint T. Allen, John C.Morris, and Zhong Chen
62. Molecular oncology of basal cell carcinomas 693Ervin H. Epstein, Jr.
63. Melanoma 698Adina Vultur, Keiran Smalley, and Meenhard Herlyn
Part 3.4 Molecular pathology: endocrinecancers
64. Oncogenic events and therapeutic targets inthyroid cancer 704James A. Fagin and Julio C. Ricarte Filho
65. The parathyroid glands 712Edward M. Brown and Andrew Arnold
66. Multiple endocrine neoplasia type 2 (MEN2) 720Jo W. M. Hoppener and C. J. M. Lips
Part 3.5 Molecular pathology: adult sarcomas67. Sarcomas 731
Lee J. Helman
Part 3.6 Molecular pathology: lymphoma andleukemia
68. Molecular pathology of lymphoma 738Christof Schneider, Laura Pasqualucci, and RiccardoDalla-Favera
69. Themolecular basis of acute myeloid leukemia 751Kim L. Rice, Monica Buzzai, Jessica Altman, andJonathan D. Licht
70. Molecular oncology of acute promyelocyticleukemia (APL) 769Valerie Lallemand-Breittenbach and HuguesdeThe
71. Acute lymphoblastic leukemia (ALL) 777Ido Paz-Priel and Alan D. Friedman
72. B-cell chronic lymphocytic leukemia 786Francesco Bertoni, Francesco Forconi, Michele Dal-Bo,Antonella Zucchetto, Riccardo Bomben, Giovanni DelPoeta, and Valter Gattei
73. Chronic myeloid leukemia: imatinib andnext-generation ABL inhibitors 793Charles L. Sawyers
74. Multiple myeloma 799W. Michael Kuehl and P. Leif Bergsagel
75. EMS: the 8p11myeloproliferative syndrome 809Donald H. C. Macdonald, Andreas Reiter, and NicholasC. P. Cross
76. JAK2 andmyeloproliferative neoplasms 818Ross L. Levine
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Cambridge University Press978-0-521-87662-9 - Molecular Oncology: Causes of Cancer and Targets for TreatmentEdited by Edward P. Gelmann, Charles L. Sawyers and Frank J. Rauscher IIIFrontmatterMore information
Contents
Part 3.7 Molecular pathology: pediatricsolid tumors
77. Pediatric solid tumors: embryonal celloncogenesis 826Jeffrey A. Toretsky and Aerang Kim
Part 4 Pharmacologic targeting of oncogenicpathways
78. Oncology drug discovery for biologics: antibodydevelopment strategies and considerations 836Bryan C. Barnhart, Marco M. Gottardis, and Matthew V.Lorenzi
79. Targeting the EGFR family of receptor tyrosinekinases 843Siyuan Zhang and Dihua Yu
80. Therapeutic approaches with antibodies tocell-surface receptors 854Antonio Gualberto
81. Signal transduction in tumor angiogenesis 861Timothy Hla, Nasser Altorki, and Vivek Mittal
82. Tyrosine-kinase inhibitors in oncology 872Anne S. Tsao, Vassiliki Papadimitrakopoulou, andRoy S. Herbst
83. Anti-estrogens and selective estrogen-receptormodulators 884Ping Fan and V. Craig Jordan
84. Therapeutic applications of anti-sensemechanismsfor the treatment of cancer 893A. Robert MacLeod and C. Frank Bennett
85. Induction of apoptosis 903Dario C. Altieri
86. DNA-methylation inhibitors 908Jean-Pierre Issa
87. Histone deacetylase inhibitor 912Paul A. Marks
88. Drug resistance: as complex and diverse as thedisease itself 921Antonio Tito Fojo
89. Molecular profiling and therapeuticdecision-making: the promise of personalizedmedicine 929Susan M. Henshall and Andrew V. Biankin
90. DNA repair inhibition in anti-cancertherapeutics 936Brian M. Alexander and Alan D. D’Andrea
Index 945
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Cambridge University Press978-0-521-87662-9 - Molecular Oncology: Causes of Cancer and Targets for TreatmentEdited by Edward P. Gelmann, Charles L. Sawyers and Frank J. Rauscher IIIFrontmatterMore information
Contributors
Byungchan AhnDepartment of Life Sciences, University of Ulsan, Ulsan,Korea
Donna G. AlbertsonHelen Diller Family Comprehensive Cancer Center,University of California San Francisco, San Francisco,CA, USA
Brian M. AlexanderDepartment of Radiation Oncology, Dana-Farber CancerInstitute, Harvard Medical School, Boston, MA, USA
Clint T. Allen, MDHead and Neck Surgery Branch, National Institute onDeafness and Other Communication Disorders, NIH,Bethesda, MD, USA
Dario C. Altieri, MDTheWistar Institute, Philadelphia, PA, USA
Jessica AltmanDivision of Hematology/Oncology, Robert H. LurieComprehensive Cancer Center, Northwestern UniversityFeinberg School of Medicine, Chicago, IL, USA
Nasser AltorkiDepartment of Cardiothoracic Surgery and NeubergerBerman Lung Cancer Research Center, Weill Medical Collegeof Cornell University, New York, NY, USA
Valsamo K. Anagnostou, MDDepartment of Pathology, Yale University School of Medicine,New Haven, CT, USA
Shira AnziDepartment of Developmental Biology and Cancer Research,IMRIC, The Hebrew University – Hadassah Medical School,Jerusalem, Israel
Andrew Arnold, MDCenter for Molecular Medicine and Department of Geneticsand Developmental Biology, University of Connecticut Schoolof Medicine, Farmington, CT, USA
Sylvia L. AsaDepartment of Pathology and Laboratory Medicine,University of Toronto, Department of Pathology, UniversityHealth Network, Toronto, Ontario, Canada
Bryan C. BarnhartOncology Drug Discovery, Bristol-Myers Squibb, Co.,Princeton, NJ, USA
Robert C. Bast, Jr., MDDepartments of Experimental Therapeutics, GynecologicMedical Oncology, Bioinformatics and ComputationalBiology, and Systems Biology, University of Texas M.D.Anderson Cancer Center, Houston, TX, USA
Vandana Batra MDCenter for Childhood Cancer Research, Department ofPediatrics, Childrens Hospital of Philadelphia, Philadelphia,PA, USA
C. Frank BennettDepartment of Antisense Drug Discovery, IsisPharmaceuticals, Inc., Carlsbad, CA, USA
P. Leif Bergsagel, MDDivision of Hematology-Oncology, Comprehensive CancerCenter, Mayo Clinic, Scottsdale, AZ, USA
Francesco BertoniLymphoma and Genomics Research Program, Institute ofOncology Research, and Lymphoma Unit, Oncology Instituteof Southern Switzerland, Bellinzona, Switzerland
Yansong Bian, MD, PhDLaboratory of Cell and Developmental Biology, NationalInstitute of Dental and Craniofacial Research, NIH, Bethesda,MD, USA
Andrew V. Biankin MB, BS, FRACS, PhDCancer Research Program, Garvan Institute of MedicalResearch, Darlinghurst, Sydney, NSW, Australia
Mary-Ann BjornstiDepartment of Pharmacology and Toxicology, University ofAlabama at Birmingham, Birmingham AL, USA
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Cambridge University Press978-0-521-87662-9 - Molecular Oncology: Causes of Cancer and Targets for TreatmentEdited by Edward P. Gelmann, Charles L. Sawyers and Frank J. Rauscher IIIFrontmatterMore information
List of contributors
Vilhelm A. BohrLaboratory of Molecular Gerontology, GerontologyResearch Center, National Institute on Aging, NIH,Baltimore, MD, USA
Riccardo BombenClinical and Experimental Onco-Hematology Unit,Centro di Riferimento Oncologico, I.R.C.C.S., Aviano,Pordenone, Italy
Donald P. BottaroUrologic Oncology Branch, Center for Cancer Research,National Cancer Institute, National Institutes of Health,Bethesda, MD, USA
Ryan J. BourgoKimmel Cancer Center, Department of Cancer Biology,Thomas Jefferson University, Philadelphia, PA, USA
Edward M. Brown, MDDivision of Endocrinology, Diabetes, and Hypertension,Brigham andWomen’s Hospital, Boston, MA, USA
Dennis K. BurnsDepartment of Pathology, University of Texas SouthwesternMedical Center, Dallas, TX, USA
Lisa M. ButlerDame Roma Mitchell Cancer Research Laboratories,Adelaide University/Hanson Institute, Adelaide, SouthAustralia
Monica BuzzaiNovartis, Origgio, VA, Italy
George A. Calin, MA, PhDRNA Interference and Non-coding RNA Center and theDepartment of Experimental Therapeutics, Universityof Texas, M.D. Anderson Cancer Center, Houston, TX,USA
Lewis C. Cantley, PhDWeill Cornell Cancer Center, New York – PresbyterianHospital, Weill Cornell Medical College, New York, NY,USA
Fabiola CecchiUrologic Oncology Branch, Center for Cancer Research,National Cancer Institute, National Institutes of Health,Bethesda, MD, USA
Margaret M. CenteneraDame Roma Mitchell Cancer Research Laboratories, AdelaideUniversity/Hanson Institute, Adelaide, South Australia
DuyKhanh P. Ceppa, MDDivision of Thoracic Surgery, Indiana University School ofMedicine, Indianapolis, IN, USA
Timothy A. ChanMemorial Sloan Kettering Cancer Center, New York, NY, USA
Zhong Chen, MD, PhDHead and Neck Surgery Branch, National Institute onDeafness and Other Communication Disorders, NIH,Bethesda, MD, USA
Derek Y. Chiang, PhDNovartis Institutes for Biomedical Research, Cambridge, MA,USA
Michael D. ColeDepartments of Pharmacology and Genetics, DartmouthMedical School, Norris Cotton Cancer Center, Lebanon, NH,USA
Kevin D. Courtney, MD, PhDDivision of Hematology/Oncology, UT Southwestern MedicalCenter, Dallas, TX, USA
Adrienne D. Cox, PhDDepartments of Radiation Oncology and Pharmacology,Lineberger Comprehensive Cancer Center, University ofNorth Carolina at Chapel Hill, Chapel Hill, NC, USA
Nicholas C. P. CrossWessex Regional Genetics Laboratory, University ofSouthampton, Salisbury District Hospital, Salisbury, UK
Thomas A. D’Amico, MDDivision of Thoracic Surgery, Duke University Health System,Durham, NC, USA
Alan D. D’AndreaDepartment of Radiation Oncology, Dana-FarberCancer Institute, Harvard Medical School, Boston,MA, USA
Michele Dal-BoClinical and Experimental Onco-Hematology Unit,Centro di Riferimento Oncologico, I.R.C.C.S., Aviano,Pordenone, Italy
Riccardo Dalla-Favera, MDDepartment of Genetics and Development, Department ofPathology and Cell Biology, and Department of Microbiologyand Immunology, Institute for Cancer Genetics and HerbertIrving Comprehensive Cancer Center, Columbia University,New York, NY, USA
Altaf A. DarCalifornia Pacific Medical Center Research Institute, SanFrancisco, CA, USA
Rachel S. DarkenDepartment of Neurology, Washington University School ofMedicine, St. Louis, MO, USA
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Cambridge University Press978-0-521-87662-9 - Molecular Oncology: Causes of Cancer and Targets for TreatmentEdited by Edward P. Gelmann, Charles L. Sawyers and Frank J. Rauscher IIIFrontmatterMore information
List of contributors
Kaustubh DattaDepartment of Urologic Research, Biochemistry andMolecular Biology, Mayo Clinic Cancer Center, Mayo ClinicFoundation, Rochester, MN, USA
Hugues de TheCNRS 7212, Universite Paris Diderot, Paris, France
Jeffry L. DeanKimmel Cancer Center, Department of Cancer Biology,Thomas Jefferson University, Philadelphia, PA, USA
Molly J. DeCristoDepartment of Biology, University of North Carolina atChapel Hill, Chapel Hill, NC, USA
Giovanni Del PoetaDepartment of Hematology, S. Eugenio Hospital andUniversity of Tor Vergata, Rome, Italy
Rebecca J. Deyell MDCenter for Childhood Cancer Research, Department ofPediatrics, Childrens Hospital of Philadelphia, Philadelphia,PA, USA
Colin P. Dinney MDDepartment of Urology, The University of Texas M. D.Anderson Cancer Center, Houston, TX, USA
John DoorbarDivision of Virology, National Institute for Medical Research,London, UK
Wael El-Rifai, MD, PhDDepartment of Surgery and Vanderbilt-Ingram Cancer Center,Vanderbilt University Medical Center, Nashville, TN, USA
Ervin H. Epstein, JrChildren’s Hospital Oakland Research Institute, Oakland, CA,USA
Shereen EzzatDepartment of Medicine, University of Toronto andthe Princess Margaret Cancer Center, University HealthNetwork, Toronto, Ontario, Canada
James A. Fagin, MDDepartment of Medicine and Human Oncology andPathogenesis Program, Memorial Sloan-Kettering CancerCenter, New York, NY, USA
Jian-Bing FanIllumina, Inc., San Diego, CA, USA
Ping FanVincent T. Lombardi Comprehensive Cancer Center,Georgetown University, DC, USA
Julio C. Ricarte FilhoDepartment of Medicine and Human Oncology andPathogenesis Program, Memorial Sloan-Kettering CancerCenter, New York, NY, USA
Jeffrey FisherIllumina, Inc., San Diego, CA, USA
Antonio Tito Fojo, MD, PhDMedical Oncology Branch and Affiliates Head, ExperimentalTherapeutics Section, Center for Cancer Research, NationalCancer Institute, Bethesda, MD, USA
Francesco ForconiDivision of Hematology and Transplant, Department ofClinical Medicine and Immunological Sciences, University ofSiena, Italy
Errol C. FriedbergLaboratory of Molecular Pathology, Department of Pathology,University of Texas Southwestern Medical Center, Dallas, TX,USA
Alan D. Friedman, MDDepartments of Oncology and Pediatrics, Division of PediatricOncology, Johns Hopkins University, Baltimore, MD, USA
Kyle A. Furge, PhDLaboratory of Computational Biology, Van Andel ResearchInstitute, Grand Rapids, MI, USA
Alexandra K. GardinoDavid H. Koch Institute for Integrative Cancer Research,Massachusetts Institute of Technology, Cambridge, MA,USA
Valter GatteiClinical and Experimental Onco-Hematology Unit, Centro diRiferimento Oncologico, I.R.C.C.S., Aviano, Pordenone, Italy
Edward P. Gelmann, MDDepartments of Medicine and Pathology, Herbert IrvingComprehensive Cancer Center, Columbia University, NewYork, NY, USA
Paramita GhoshDepartments of Biochemistry and Molecular Medicine, andUrology, University of California David School of Medicine,Sacramento, and VA Northern Health Care System, Mather,CA, USA
Elizabeth L. GosnellKimmel Cancer Center, Department of Cancer Biology,Thomas Jefferson University, Philadelphia, PA, USA
Marco M. GottardisOncology Drug Discovery, Bristol-Myers Squibb, Co.,Princeton, NJ, USA
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Cambridge University Press978-0-521-87662-9 - Molecular Oncology: Causes of Cancer and Targets for TreatmentEdited by Edward P. Gelmann, Charles L. Sawyers and Frank J. Rauscher IIIFrontmatterMore information
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Jennifer GrandisUniversity of Pittsburgh Medical Center, Pittsburgh, PA,USA
Joanna GrodenDepartment of Molecular Virology, Immunology, and MedicalGenetics, The Ohio State University College of Medicine,Columbus, OH, USA
Antonio Gualberto MD PhDDepartment of Pathology and Laboratory Medicine, TheAlpert Medical School of Brown University, Providence, RI,USA
David H. Gutmann, MD, PhDDepartment of Neurology, Washington University School ofMedicine, St. Louis, MO, USA
Samir HanashFred Hutchinson Cancer Research Center, Seattle, WA, USA
J. Marie HardwickFeinstone Department of Molecular Microbiology andImmunology, Johns Hopkins University, Bloomberg School ofPublic Health, Baltimore, MD, USA
Ruth HeLombardi Comprehensive Cancer Center, GeorgetownUniversity, Washington DC, USA
Carl-Henrik HeldinLudwig Institute for Cancer Research, Uppsala University,Uppsala, Sweden
Lee J. Helman, MDCenter for Cancer Research, National Cancer Institute,Bethesda, MD, USA
Bryan T. Hennessy, MDDepartments of Experimental Therapeutics, GynecologicMedical Oncology, Bioinformatics and ComputationalBiology, and Systems Biology, University of Texas M.D.Anderson Cancer Center, Houston, TX, USA
Susan M. Henshall, PhDCancer Research Program, Garvan Institute of MedicalResearch, Darlinghurst, Sydney, NSW, Australia
Roy S. Herbst, MD, PhDYale University School of Medicine, New Haven, CT
Meenhard HerlynTheWistar Institute Melanoma Research Center, Philadelphia,PA, USA
Theresa E. HickeyDame Roma Mitchell Cancer Research Laboratories,Adelaide University/Hanson Institute, Adelaide, SouthAustralia
Timothy HlaCenter of Vascular Biology, Department of Pathology andLaboratory Medicine, Weill Medical College of CornellUniversity, New York, NY, USA
Jo W. M. HoppenerDepartment of Molecular Cancer Research, UniversityMedical Center Utrecht, University Hospital, the Netherlands
Yujin Hoshida, MD, PhDLiver Cancer Program, Tisch Cancer Institute, Division ofLiver Diseases, Icahn School of Medicine at Mount Sinai, NewYork, NY, USA
Nancy E. HynesFriedrich Miescher Institute for Biomedical Research, Basel,Switzerland
Rosalyn B. IrbyPenn State Hershey Cancer Institute H046, Penn StateUniversity College of Medicine, Hershey, PA, USA
Jean-Pierre IssaFels Institute for Cancer Research, Temple University Schoolof Medicine, Philadelphia, PA, USA
Yoshiaki Ito, MD PhDCancer Science Institute, National University of Singapore,Center for Translational Medicine, Singapore
V. Craig JordanVincent T. Lombardi Comprehensive Cancer Center,Georgetown University, DC, USA
Richard Jove, PhDBeckham Research Institute, City of Hope, Duarte, CA,USA
Michael KarinLaboratory of Gene Regulation and Signal Transduction,Department of Pharmacology and Pathology, MooresCancer Center, UCSD School of Medicine, La Jolla,CA, USA
Masaru Katoh, MD, PhDGenetics and Cell Biology Section, National Cancer Center,Tokyo, Japan
Aerang KimDepartment of Pediatrics, Children’s National Medical Center,George Washington University, Washington, DC, USA
Erik S. KnudsenDepartment of Pathology, UT Southwestern Medical Center,Dallas, TX, USA
Chuay-Yeng KooDepartment of Surgery and Cancer, Imperial College London,Hammersmith Hospital Campus, London, UK
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Cambridge University Press978-0-521-87662-9 - Molecular Oncology: Causes of Cancer and Targets for TreatmentEdited by Edward P. Gelmann, Charles L. Sawyers and Frank J. Rauscher IIIFrontmatterMore information
List of contributors
Wolfgang J. KostlerDepartment of Biological Regulation, TheWeizmann Instituteof Science, Rehovot, Israel
W.Michael Kuehl, MDCancer Genetics Branch, Center for Cancer Research, NationalCancer Institute, Bethesda, MD, USA
Hsing-Jien KungDepartments of Biochemistry and Molecular Medicine, andUrology, University of California David School of Medicine,Sacramento, CA, USA
Chang-Hyuk KwonDepartment of Developmental Biology, University of TexasSouthwestern Medical Center, Dallas, TX, USA; Solid TumorProgram and Department of Neurological Surgery, JamesComprehensive Cancer Center, The Ohio State UniversityWexner Medical Center, Columbus, OH, USA
Abizar LakdawallaIllumina, Inc., San Diego, CA, USA
Valerie Lallemand-BreittenbachCNRS 7212, Universite Paris Diderot, Paris, France
Eric W.-F. LamDepartment of Surgery and Cancer, Imperial College London,Hammersmith Hospital Campus, London, UK
Jill E. Larsen, PhDHamon Center for Therapeutic Oncology Research, SimmonsCancer Center, University of Texas Southwestern MedicalCenter, Dallas, TX, USA
Shun J. LeeDivision of Hematology-Oncology, Department of Medicine,Moores Cancer Center, University of California, San Diego, LaJolla, CA, USA
Young H. LeeUrologic Oncology Branch, Center for Cancer Research,National Cancer Institute, National Institutes of Health,Bethesda, MD, USA
Ross L. Levine, MDHuman Oncology and Pathogenesis Program, LeukemiaService, Department of Medicine, Memorial Sloan-KetteringCancer Center, New York, NY, USA
Ying LiThe University of Texas, M.D. Anderson Cancer Center,Houston, TX, USA
Siong-Seng Liau, MD, FRCSHepatopancreatobiliary Surgery Unit, Department of Surgery,Addenbrooke’s Hospital, and Medical Research CouncilCancer Cell Unit, Hutchison-MRC Research Center,University of Cambridge, Cambridge, UK
Jonathan D. Licht, MDDivision of Hematology/Oncology, Robert H. LurieComprehensive Cancer Center, Northwestern UniversityFeinberg School of Medicine, Chicago, IL, USA
C. J. M. LipsDepartment of Internal Medicine, University Medical CenterUtrecht, Utrecht, the Netherlands
Josep M. Llovet, MDLiver Cancer Program, Division of Liver Diseases, IcahnSchool of Medicine at Mount Sinai, New York, NY, USA; andBCLC Group, IDIBAPS, CIBEREHD, Liver Unit, HospitalClınic, Barcelona, Spain
Leendert H. J. LooijengaDepartment of Pathology, Erasmus MC – University MedicalCenter Rotterdam, Daniel den Hoed Cancer Center, JosephineNefkens Institute, Rotterdam, the Netherlands
Matthew V. LorenziOncology Drug Discovery, Bristol-Myers Squibb, Co.,Princeton, NJ, USA
Yongde LuoCenter for Cancer and Stem Cell Biology, Institute ofBiosciences and Technology, Texas A&MHealth ScienceCenter, Houston, TX, USA
Donald H. C. MacdonaldDepartment of Haematology, Imperial College, London,UK
GwenMacDonaldFriedrich Miescher Institute for Biomedical Research, Basel,Switzerland
A. Robert MacLeodDepartment of Antisense Drug Discovery, IsisPharmaceuticals, Inc., Carlsbad, CA, USA
A. Kathleen McClendonKimmel Cancer Center, Department of Cancer Biology,Thomas Jefferson University, Philadelphia, PA, USA
Wallace L. McKeehanCenter for Cancer and Stem Cell Biology, Institute ofBiosciences and Technology, Texas A&MHealth ScienceCenter, Houston, TX, USA
John M. Maris MDCenter for Childhood Cancer Research, Department ofPediatrics, Childrens Hospital of Philadelphia, Philadelphia,PA, USA
Paul A. MarksCell Biology and Genetics Program, Sloan-Kettering Institutefor Cancer Research, Memorial Sloan-Kettering CancerCenter, New York, NY, USA
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Soheil MeshinchiClinical Research Division, Fred Hutchinson Cancer ResearchCenter, Seattle, WA, USA
Gordon B. Mills, MD, PhDDepartments of Experimental Therapeutics, GynecologicMedical Oncology, Bioinformatics and ComputationalBiology, and Systems Biology, University of Texas M.D.Anderson Cancer Center, Houston, TX, USA
John D. Minna, MDHamon Center for Therapeutic Oncology Research, SimmonsCancer Center University of Texas Southwestern MedicalCenter, Dallas, TX, USA
Lopa MishraThe University of Texas, M.D. Anderson Cancer Center,Houston, TX, USA
Vivek MittalDepartment of Cardiothoracic Surgery and NeubergerBerman Lung Cancer Research Center, and Department ofCell and Developmental Biology, Weill Medical College ofCornell University, New York, NY, USA
Nicole L. MooreDame Roma Mitchell Cancer Research Laboratories, AdelaideUniversity/Hanson Institute, Adelaide, South Australia
John C. Morris, MDMetabolism Branch, National Cancer Institute, NIH, Bethesda,MD, USA
Kyle W. MuirDepartment of Surgery and Cancer, Imperial College London,Hammersmith Hospital Campus, London, UK
Karl MungerBrigham andWomen’s Hospital, Harvard Medical School,Boston, MA, USA
Willscott E. NauglerOregon Health and Sciences University, Department ofMedicine, Division of GI and Hepatology, Portland, OR,USA
Milena S. NicolosoRNA Interference and Non-coding RNA Center and theDepartment of Experimental Therapeutics, Universityof Texas, M.D. Anderson Cancer Center, Houston, TX,USA
Moriah H. NissanHuman Oncology and Pathogenesis Program, and Louis V.Gerstner Jr. Graduate School of Biomedical Sciences,Memorial Sloan-Kettering Cancer Center, New York, NY,USA
Benjamin F. O’ConnorDivision of Hematology-Oncology, Department of Medicine,Moores Cancer Center, University of California, San Diego, LaJolla, CA, USA
Kenneth OffitDepartment of Medicine, Clinical Genetics Service, MemorialSloan-Kettering Cancer Center, New York, NY, USA
J. Wolter OosterhuisDepartment of Pathology, Erasmus MC – University MedicalCenter Rotterdam, Daniel den Hoed Cancer Center, JosephineNefkens Institute, Rotterdam, the Netherlands
Arne OstmanCancer Center Karolinska, Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden
Vassiliki PapadimitrakopoulouUniversity of Texas M.D. Anderson Cancer Center, Houston,TX, USA
Luis F. ParadaDepartment of Developmental Biology, University ofTexas Southwestern Medical Center, Dallas, TX, USA
Laura Pasqualucci, MDInstitute for Cancer Genetics and Herbert IrvingComprehensive Cancer Center, Columbia University, NewYork, NY, USA
Ido Paz-Priel, MDDepartments of Oncology and Pediatrics, Division ofPediatric Oncology, Johns Hopkins University, Baltimore,MD, USA
Erin M. PerchiniakDepartment of Molecular Virology, Immunology, and MedicalGenetics, The Ohio State University College of Medicine,Columbus, OH, USA
Richard G. PestellDepartment of Cancer Biology, Kimmel Cancer Center,Thomas Jefferson University, Philadelphia, PA, USA
Daniel PinkelHelen Diller Family Comprehensive Cancer Center,University of California San Francisco, San Francisco,CA, USA
Michael Pollak, MDDepartment of Oncology, McGill University, Montreal,Quebec, Canada
Marshall R. PosnerMount Sinai Medical Center, Tisch Cancer Institute, IcahnSchool of Medicine, New York, NY, USA
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Karen PulfordNuffield Division of Clinical Laboratory Sciences, RadcliffeDepartment of Medicine, University of Oxford, Oxford, UK
Yun QiuDepartment of Pharmacology and Experimental Therapeutics,University of Maryland School of Medicine, Baltimore, MD,USA
Kelly QuesnelleUniversity of Pittsburgh Medical Center, Pittsburgh, PA, USA
Andreas ReiterMedizinische Klinik, Universatsmedizin Mannheim, Germany
Marsha ReyngoldMemorial Sloan-Kettering Cancer Center, New York, NY, USA
Kim L. RiceDivision of Hematology/Oncology, Robert H. LurieComprehensive Cancer Center, Northwestern UniversityFeinberg School of Medicine, Chicago, IL, USA
Thomas Ried, MDSection of Cancer Genomics, Genetics Branch, Center forCancer Research /NCI/NIH, Bethesda, MD, USA
David L. RimmMD, PhDDepartment of Pathology, Yale University School of Medicine,New Haven, CT, USA
Mostafa RonaghiIllumina, Inc., San Diego, CA, USA
Charles L. Sawyers, MDHoward Hughes Medical Institute, Chevy Chase, MD, andHuman Oncology and Pathogenesis Program, MemorialSloan-Kettering Cancer Center, New York, NY, USA
Christof Schneider, MDInstitute for Cancer Genetics and Herbert IrvingComprehensive Cancer Center, Columbia University, NewYork, NY, USA
Roger A. SchultzSignature Genomics, Spokane, WA, USA
Vikas SehdevDepartment of Surgery and Vanderbilt-Ingram Cancer Center,Vanderbilt University Medical Center, Nashville, TN, USA
Sohela ShahDepartment of Medicine, Clinical Genetics Service, MemorialSloan-Kettering Cancer Center, New York, NY, USA
Eitan ShaulianDepartment of Biochemistry and Molecular Biology, IMRIC,The Hebrew University – Hadassah Medical School, Jerusalem,Israel
Jerry W. ShayUniversity of Texas Southwestern Medical Center, Departmentof Cell Biology, Dallas, TX, USA
Yosef ShilohThe David and Inez Myers Laboratory for Genetic Research,Department of Human Molecular Genetics and Biochemistry,Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
Keiran SmalleyDepartment of Molecular Oncology, H. Lee Moffitt CancerCenter and Research Institute, Tampa, FL, USA
David B. Solit, MDHuman Oncology and Pathogenesis Program, Department ofMedicine, Memorial Sloan-Kettering Cancer Center, NewYork, NY, USA
Allan D. SpigelmanUNSW St Vincent’s Clinical School, Cancer Services, StVincent’s & Mater Health, Sydney, Hereditary Cancer Clinic,St Vincent’s Hospital, The Kinghorn Cancer Centre, Sydney,NSW, Australia
Zsofia K. StadlerDepartment of Medicine, Clinical Genetics Service, MemorialSloan-Kettering Cancer Center, New York, NY, USA
Tinna StevnsnerDanish Centre for Molecular Gerontology and Danish AgingResearch Center, University of Aarhus, Department ofMolecular Biology, Denmark
Derek L. StirewaltClinical Research Division, Fred Hutchinson Cancer ResearchCenter, Seattle, WA, USA
Scott A. StuartDivision of Hematology-Oncology, Department of Medicine,Moores Cancer Center, University of California, San Diego, LaJolla, CA, USA
Grace K. Suh, MDDepartments of Experimental Therapeutics, GynecologicMedical Oncology, Bioinformatics and ComputationalBiology, and Systems Biology, University of Texas M.D.Anderson Cancer Center, Houston, TX, USA
Robert S. SvatekDepartment of Urology, the University of Texas M. D.Anderson Cancer Center, Houston, TX, USA
Ayumu TaguchiFred Hutchinson Cancer Research Center, Seattle, WA, USA
Bin T. Teh, MD, PhDNational Cancer Centre of Singapore, Duke-NUS GraduateMedical School, Singapore, and Cancer Science Institute ofSingapore
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Xinchen TengFeinstone Department of Molecular Microbiology andImmunology, Johns Hopkins University, Bloomberg School ofPublic Health, Baltimore, MD, USA
Lifeng TianDepartment of Cancer Biology, Kimmel Cancer Center,Thomas Jefferson University, Philadelphia, PA, USA
Wayne D. TilleyDame Roma Mitchell Cancer Research Laboratories, AdelaideUniversity/Hanson Institute, Adelaide, South Australia
Donald J. TindallDepartment of Urologic Research, Biochemistry andMolecular Biology, Mayo Clinic Cancer Center, Mayo ClinicFoundation, Rochester, MN, USA
Jeffrey A. ToretskyDepartments of Oncology and Pediatrics, GeorgetownUniversity, Washington, DC, USA
Anne S. TsaoUniversity of Texas M.D. Anderson Cancer Center, Houston,TX, USA
David A. Tuveson, MD, PhDDepartment of Oncology, Addenbrooke’s Hospital, Universityof Cambridge, Cambridge, UK
Robert C. A. M. vanWaardenburgDepartment of Pharmacology and Toxicology, University ofAlabama at Birmingham, Birmingham, AL, USA
Carter VanWaes, MD, PhDHead and Neck Surgery Branch, National Institute onDeafness and Other Communication Disorders, NIH,Bethesda, MD, USA
Roeland Verhaak, PhDDepartments of Experimental Therapeutics, GynecologicMedical Oncology, Bioinformatics and ComputationalBiology, and Systems Biology, University of Texas M.D.Anderson Cancer Center, Houston, TX, USA
Augusto Villanueva, MDInstitute of Liver Studies, Division of TransplantationImmunology andMucosal Biology, King’s College London, UK
Adina VulturTheWistar Institute Melanoma Research Center, Philadelphia,PA, USA
ChenguangWangDepartment of Stem Cell Biology and Regenerative Medicine,Kimmel Cancer Center, Thomas Jefferson University,Philadelphia, PA, USA
FenWangCenter for Cancer and Stem Cell Biology, Institute ofBiosciences and Technology, Texas A&MHealth ScienceCenter, Houston, TX, USA
Jean Y. J. WangDivision of Hematology-Oncology, Department of Medicine,Moores Cancer Center, University of California, San Diego, LaJolla, CA, USA
Ling-YuWangDepartments of Biochemistry and Molecular Medicine,University of California David School of Medicine,Sacramento, CA, USA
Janindra WarusavitarneDepartment of Surgery, St Mark’s Hospital, Harrow,Middlesex, UK
JodyWhiteFrank Reidy Research Center for Bioelectrics, Old DominionUniversity, Norfolk, VA, USA
Woodring E. WrightUniversity of Texas Southwestern Medical Center, Departmentof Cell Biology, Dallas, TX, USA
Michael B. YaffeDavid H. Koch Institute for Integrative Cancer Research andDepartment of Biological Engineering, Massachusetts Instituteof Technology, Cambridge, MA, USA
Ji-Yeon Yang, PhDDepartments of Experimental Therapeutics, GynecologicMedical Oncology, Bioinformatics and ComputationalBiology, and Systems Biology, University of Texas M.D.Anderson Cancer Center, Houston, TX, USA
Yosef YardenDepartment of Biological Regulation, TheWeizmann Instituteof Science, Rehovot, Israel
Timothy J. Yeatman, MDGibbs Cancer Center and Research Institute, Spartanburg, SC,USA
Khay Guan Yeoh, MBBS, FRCP, FRCP (Glasg)Department of Medicine, Yong Loo Lin School of Medicine,National University of Singapore and National UniversityHealth System, Singapore
Dihua Yu, MD, PhDUniversity of Texas, M.D. Anderson Cancer Center, Houston,TX, USA
Hua Yu, PhDBeckham Research Institute, City of Hope, Duarte, CA, USA
Siyuan Zhang, MD PhDUniversity of Texas, M.D. Anderson Cancer Center, Houston,TX, USA
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Xuemin ZhangState Key Laboratory of Proteomics, Institute of Basic MedicalSciences, National Center of Biomedical Analysis, Beijing,China
Antonella ZucchettoClinical and Experimental Onco-Hematology Unit, Centro diRiferimento Oncologico, I.R.C.C.S., Aviano, Pordenone,Italy
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Preface
This bookwas conceivedmore than five years before its publica-tion date. It was intended to provide a resource that summarizedtechnology, biochemistry, molecular pathophysiology, and tar-geted therapeutics. As contributors were being recruited andchapters written the field that was being described changed atan accelerating pace. It is a tribute to scientific progress that vol-umes like this are out-of-date as they are published, but bookslike this are not meant to contain the most current laboratorydiscovery or report the most recent FDA approval.
While this book was being written there have been majoradvances in molecular oncology. The Cancer Genome Atlas(cancergenome.nih.gov) has demonstrated the broad spectrumof mutations in an expanding list of cancers. DNA sequenceanalysis alone has demonstrated that as cancers grow, metas-tasize, and develop treatment resistance, individual tumor siteswithin a single patient evolve differently and demonstrateincreasingly complex spectra of driver and passenger muta-tions.These findings alone strongly support theDarwinian viewof tumor progression.The complexities of cellular dysregulationin cancer may arise fromDNA sequence changes, but extend toother levels of gene regulation. During the writing of this bookthe role of micro-RNAs (miRNAs) in cancer was elucidated.Aberrations in epigenetics such as DNA methylation and his-tone acetylation were demonstrated. Cancer drug developmenthas also proceeded at increasing rates. In the period 2008–2012there were 51 approvals of new drugs for cancer treatment bytheUSFood andDrugAdministration.Many of these approvals
resulted from impressive data in Phase II trials that clearlydemonstrated efficacy where no agents have worked before.
As we have assembled the contributions for this volume wehave watched as more and more information is provided andaccessed in electronic format, replacing the printed word. It isnot hard to predict that younger generations of investigatorswill dispense entirely with books and access all information onelectronic screens. Clearly a volume like this ismeant to providerapid reference when accessed from a shelf in someone’s office.
We the editors took on the task of assembling this volumeto provide background for active researchers, to provide mean-ingful lists of important citations that form the foundation ofthemolecular pathophysiology of cancer, and to define the con-text in which current investigation is pursued. This book isintended for students and professionals in academia and indus-try. Where electronic databases are non-discriminatory andweb-based searches can be overwhelming in their downloadlists, volumes like this provide the perspective and judgmentof experts who have spent a very long time in a path of studyand therefore share their understanding and viewpoints that aremissed in database or electronic literature searches. Volumeslike this collect the experience and wisdom of the contributorsand therefore provide value and perspective. As journal titlesproliferate and the scientific literature expands, it is books likethis that guide knowledge and help organize the work in a fieldinto a comprehensible narrative. We hope you find these pagesuseful.
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