CanCer researCh: a Visionary Commitment Maine Medical Center (MMC)’s tradition of biomedical research dates back more than half a century. In 1956, the first National Institutes of Health (NIH)-funded scientist was recruited to MMC, and the Institution was awarded its first NIH fellowship in 1961 and its first NIH grant in 1962. The initial decades of research at MMC resulted in the development and early adoption of such cancer-related projects as a bone marrow transplant program and the flow cytometry laboratory. In 1991, Maine Medical Center Research Institute (MMCRI) was established to build on these accomplishments and formalize the growing importance and success of research at MMC.

During the past decade, MMCRI has placed additional emphasis on cancer research at the basic mechanistic level, as well as the clinical and population health level. This commitment is driven by the concerns of its leadership and dedicated faculty to the considerable and unfortunate impact of cancer on the citizens of the state of Maine – Maine being among those states with the highest rates of cancer occurrence and cancer mortality (cancer deaths per 100,000 population) in the country. Although the explanation for this remains uncertain, the fact that Maine is the “oldest” state in the nation (with a median age of 43.5 years) is likely an important contributor. To further meet this challenge, MMCRI has enhanced its research efforts in metabolic diseases, including obesity, which is also known to be a risk factor for cancer.

Maine Medical Center Research Institute - Cancer Focus

I am from Maine. After gathering volumes of knowledge from distinguished institutions around the country, I knew what I wanted to do: I wanted to bring that knowledge back home and ensure that

any discoveries I made impacted my community, right here in Maine. – Peter Brooks, PhD: Investigator developing of novel diagnostics and therapies for cancers of the breast, lung, liver, prostate, skin.

MMCRI Cancer Research

Focus Areas of Breast, Ovary, Skin, Brain, Blood, Bone, Liver, Prostate

& Lung Cancers

Diagnostics & Early Detection

Metastasis

Therapeutics

Translational Research

Clinical Trials

Treatment Decision Making

Outcomes

Tissue Bank Optimization

Small Animal Imaging

Community Outreach & Education

PradeeP sathyanarayana, Phd –in hot Pursuit of Leukemia’s Cure

Our genes tell us volumes about where we’re from, what we are, and what may become of us. Genes live on strands of DNA. RNA translates our DNA’s genetic messages into our cells, in order to build protein, through so-called “messenger RNA”, or mRNA. These messages can say anything from “you’ve got blue eyes” to “you’ve got leukemia.” Thus began the recent focus on “gene silencing” in cancer biology. In 2006, Drs. Fire and Mello won the Nobel Prize for Medicine when they proved that mRNA can either spread a gene’s bad news or good news to the cell: In order for disease to progress it needs to receive a message from the DNA to say “Ok, time to proliferate!” However, if we kill the “messenger” (the mRNA) we could kill the disease. The breakthrough came when Fire and Mello identified a sort of DNA spy, called “microRNA,” which can be programmed to perform one of two jobs: 1) kill the messenger if it’s delivering bad news (“you’ve got leukemia”) or 2) help the messenger along if it’s delivering good news (“you DON’T have leukemia”). This leads us to the research of Pradeep Sathyanarayana, PhD, and his team at MMCRI.

Through synthesizing microRNA Dr. Sathyanarayana and his lab are working every day to silence the specific gene that causes Acute Myeloid Leukemia (AML), a tragic and devastating form of blood cancer. Each year, AML kills 75% of the nearly 14,000 individuals who develop the disease. Since our bone marrow manufactures our blood cells, Dr. Sathyanarayana has begun studying human bone marrow cells from Maine Medical Center’s own BioBank in humanized mouse models (a mouse carrying functioning human tissues; in this case, bone marrow cells). Once the bone marrow cells are implanted, he then inserts a specially designed microRNA into the bone marrow cells which, as he is on the verge of proving, will silence AML genes in humanized mouse models.

Once we can prove that we can cure leukemia in a humanized mouse, it’s only a matter of time before these novel therapies could be applied to humans. What’s more, it turns out that the same family of microRNA Dr. Sathyanarayana is making in his lab has the potential to kill the messengers not only of blood cancers, but of breast, brain and liver cancers as well. MMCRI provides the talent, the tools and the freedom for this kind of groundbreaking research, right here in Maine.

MMCRI has a well-established research program and state-of-the-art infrastructure in the area of stem cell biology and regenerative medicine. Physicians in the Hematology/Oncology Program at MMC are highly supportive of our ongoing research in AML. Therefore MMCRI has been a great place to pursue cutting edge research in AML. – Pradeep Sathyanarayana, PhD

an oVerView of mmCri CanCer researCh

The Need for Cancer Research PhilanthropyDr. Harold Varmus, Director of the National Cancer Institute (NCI), has stated: “This is a time of remarkable opportunity in cancer research. Armed with broad knowledge about how various kinds of cancer arise and with powerful new research tools, the cancer research community … is poised to reduce the burden of cancer in this country and around the world at an accelerated pace.” 1 Yet, support for cancer research by the federal government through the NCI has decreased significantly over the past dozen years and now stands at a point no greater than it was in 1999 in terms of real dollars; hence, the great importance of support from other sources.

CoLLaboration

MMCRI, with its outstanding faculty and facilities, its capabilities to conduct multidisciplinary cancer research across the biomedical spectrum from basic mechanisms to drug therapy to population health and health care delivery science, and with its strong collaborative ties with other regional research institutions (e.g. Tufts University School of Medicine, The University of Vermont, and The Jackson Laboratory, among others), is remarkably well positioned, and fully dedicated to making innovative and substantive advances in the prevention and treatment of the group of diseases that comprise cancer.

aCCess

Wonderful opportunities exist to enhance the scope and success of our cancer research efforts, particularly in the area of translational cancer therapeutics – the discovery and testing of new cancer agents. MMCRI currently conducts 112 open and active clinical trials at MMC dealing directly with cancer, supporting 1,296 enrollees to date. 184 oncology patients were enrolled here in 2014 alone, sparing

them and their families repeated travel to and from Boston for their trial therapies. On the basic science end of the spectrum, MMCRI employs 13 investigators who are actively studying cancers of the breast, ovary, skin, brain, blood, bone, liver, prostate and lung. In 2010, MMC leadership had the foresight to invest in a research catalyst,

1 The NCI’s Director’s Message. http://www.cancer.gov/aboutnci/budget_planning_leg/plan-2016/directors-message. Dec. 2, 2014.

When I relocated to this area, I was in search of guidance and a supportive research infrastructure with which I could develop and conduct my pediatric and young adult-focused clinical research. MMCRI provided just that platform and played a critical role in the cultivation and activation of my current investigator-initiated, multi-institutional trial. – Aaron Weiss, MD, PhD: Leader of a collaborative clinical trial to decrease tumor size and pain in children and young adults.

a PhD-trained scientist with a degree in Molecular Biology and experience conducting research in a clinical oncology setting. The activities of this investigator advance laboratory discoveries into the clinic (20 active, cancer-related projects, to date) with the ultimate goal of improving patient health.

22 Bramhall StreetPortland, ME 04102

www.mmcri.org

Continued success in this arena requires a group of dedicated and experienced medical research oncologists - physician investigators who would work in partnership with our basic scientists, our health services researchers, and our research catalysts to bring laboratory discoveries from MMCRI and other research institutions to our patients and the people of the state of Maine and the nation. The infrastructure and facilities are currently in place to take advantage of such expertise as it becomes available, and take a dramatic step forward in the fight against cancer. To achieve this vision, we are actively recruiting world class physician scientists to join our team. This is a top priority of our Research Master Plan launched in 2013 and will position MMCRI to both shape and better participate in the national cancer research agenda, and importantly, allow MMC to markedly enhance the availability of the very latest cancer diagnostics, therapeutics and personalized treatment and preventative strategies to the people of Maine.

CanCer researCh Vision for a Cure

Cancer Research and the Unique Role of a Translational Research CatalystThe MMCRI Research Catalyst is a PhD-trained scientist with a degree in Molecular Biology and experience conducting research in a clinical oncology setting. This scientist is skilled in clinical research design and methodology, in team science and in identifying the clinical implications of laboratory-based research. The catalyst furthers cancer research by proactively crafting, organizing and managing multidisciplinary and multi-institutional translational research projects. Since the introduction of the catalyst, MMC has seen an increase in the number of cancer translational projects driven by multi-investigator teams. This includes basic scientists and clinicians at MMC and collaborating institutions such as the Jackson Laboratory. Many of these projects have resulted in subsequent grant awards and/or manuscripts published in peer-reviewed medical journals. The MMC catalyst has facilitated 20 cancer-related translational studies since 2010. The activities of the catalyst are a critical step in bridging the gap between bench and bedside.

CanCer CLiniCaL triaLs:184 Oncology Patients were enrolled in 2014

1,296 patients have been enrolled in the currently active studies for all of the years they have been open.

112 open and active clinical trials at MMC dealing directly with cancer.

staff inVestment:13 basic and outcomes researchers are conducting cancer research, not including the physicians involved in the 112 cancer-related clinical trials at MMC.

The environment and support

networks at MMCRI are undoubtedly more encouraging

of collaboration, rather than competition, making this a wonderful place to work and a place where true

science can flourish. – Michaela Reagan, PhD: Leading a lab dedicated to the study of cancers

originating in the bone.

For more information on how you can support cancer research at Maine Medical Center please contact Kendra F. Allen at (207) 662-2925 or kallen@mmc.org.