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UPDATE M-LINE I 800-962-3555 I mcancer.org j ANUARY 2015 Gene Sequencing Program MI-ONCOSEQ Helps Identify Cancer Mutations, Improve Treatments As advancements in cancer treatment occur over time, many patients are living longer, higher quality lives with metastatic disease. The problem for patients is that there is often no standard of care for their disease, or the standard of care has proven ineffective. At some point, treatment options run out. A program at the University of Michigan Comprehensive Cancer Center called MI-ONCOSEQ uses high-throughput gene sequencing techniques to help find new options. The multidisciplinary project stems from laboratory work led by Arul Chinnaiyan, M.D., Ph.D., and brings together a precision medicine tumor board with expertise from clinical oncology, clinical genetics, genomic science/bioinformatics, clinical pathology, social and behavior sciences, and bioethics. It uses gene sequencing results to give clinicians and patients recommendations regarding clinical trials or targeted therapy based on the molecular characteristics of an individual patient’s cancer. Since MI-ONCOSEQ launched three years ago, more than 400 adult patients and 80 pediatric patients have had their genes sequenced. “Ours is one of the few pioneering studies in this area and we hope to set the standards for the future when clinical sequencing becomes adopted as routine standard of care,” says Chinnaiyan, director of the Michigan Center for Translational Pathology. “We have made tremendous advances in just the short time since initiating our study and we hope to make a significant impact in the treatment of cancer that will greatly benefit patients.” In a study published in Science Translational Medicine, Chinnaiyan’s team found that identifying a patient’s “mutational landscape” provides a promising approach for targeting which treatments or clinical trials may best help a patient. Researchers also use the data to identify new genetic anomalies. Since the project began, researchers have made discoveries in both common tumors – a mutation in the estrogen Arul Chinnaiyan, M.D., Ph.D., David C. Smith, M.D. Continued on page four

Update January 2015

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University of Michigan Comprehensive Cancer Center newsletter for physicians. This issue includes precision medicine tumor board, endocrine oncology program and tumor bio marker research.

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Page 1: Update January 2015

U PDAT E

M-LINE I 800-962-3555 I mcancer.org

j A N U A R Y 2 0 1 5

Gene Sequencing Program MI-ONCOSEQ Helps Identify Cancer Mutations, Improve TreatmentsAs advancements in cancer treatment occur over time, many patients are living longer, higher quality lives with metastatic disease. The problem for patients is that there is often no standard of care for their disease, or the standard of care has proven ineffective. At some point, treatment options run out.

A program at the University of Michigan Comprehensive Cancer Center called MI-ONCOSEQ uses high-throughput gene sequencing techniques to help find new options.

The multidisciplinary project stems from laboratory work led by Arul Chinnaiyan, M.D., Ph.D., and brings together a precision medicine tumor board with expertise from clinical oncology, clinical genetics, genomic science/bioinformatics, clinical pathology, social and behavior sciences, and bioethics. It uses gene sequencing results to give clinicians and patients recommendations regarding clinical trials or targeted therapy based on the molecular characteristics of an individual patient’s cancer.

Since MI-ONCOSEQ launched three years ago, more than 400 adult patients and 80 pediatric patients have had their genes sequenced.

“Ours is one of the few pioneering studies in this area and we hope to set the standards for the future when clinical sequencing becomes adopted as routine standard of care,” says Chinnaiyan, director of the Michigan Center for Translational Pathology. “We have made tremendous advances in just the short time since initiating our study and we hope to make a significant impact in the treatment of cancer that will greatly benefit patients.”

In a study published in Science Translational Medicine, Chinnaiyan’s team found that identifying a patient’s “mutational landscape” provides a promising approach for targeting which treatments or clinical trials may best help a patient. Researchers also use the data to identify new genetic anomalies.

Since the project began, researchers have made discoveries in both common tumors – a mutation in the estrogen

Arul Chinnaiyan, M.D., Ph.D., David C. Smith, M.D.

Continued on page four

Page 2: Update January 2015

subspecialty,

M-LINE I 800-962-3555 I mcancer.org

potential new oral drug for adrenal cancer, ATR-101, that is currently being tested in a phase 1 trial at U-M and other centers. In addition to the ATR-101 trial, the Endocrine Oncology clinical research team, directed by Richard Auchus, M.D., Ph.D., offers five other clinical trials for adrenal and thyroid cancers.

Clinical studies focusing on the epidemiology, genetics and outcome are critical to finding effective treatment options for patients with these rare cancers. The U-M endocrine oncology program has demonstrated success in fostering collaborative efforts between institutional and international teams of investigators. This includes integral involvement in three collaborative endocrine cancer projects through The Cancer Genome Atlas, a program of the National Cancer Institute and the National Human Genome Research Institute that aims to characterize and analyze the genome of specific tumors. Because of these collaborations, TCGA agreed to include adrenal cancer, phenochromocytoma and thyroid cancer in their genomic platform.

A recent comprehensive analysis of thyroid cancer from the TCGA identified markers of aggressive tumors, which could allow for better targeting of appropriate treatments to individual patients. The researchers, led by U-M pathologist Tom Giordano, M.D., Ph.D., suggest reclassifying thyroid cancer based on genetic markers, which could move the disease into a position to benefit more from precision

Endocrine cancers are among the most rare. They range from the often treatable thyroid cancer to the often deadly adrenal cancer. At the University of Michigan Comprehensive Cancer Center the endocrine sub-specialists are leading the way in working towards making all endocrine cancers curable.

What started as a team of six physicians decades ago, has grown today to include more than 20 faculty-clinicians and scientists leading basic and translational research programs, participating in all phases of clinical trials to provide patients with adrenal cancer, neuroendocrine tumors (NETs) and thyroid cancer with cutting edge care. The multi-disciplinary Endocrine Oncology team is led by Gary D. Hammer, M.D., Ph.D., and includes endocrinologists, endocrine surgeons, oncologists, geneticists, radiologists, nuclear medicine specialists, pathologists, radiation oncologists, nurse practitioners and nurses.

Patients come to U-M from around the world for access to the latest treatment options, including many investigational therapies developed by our Endocrine Oncology faculty. For example, Ron Koenig, M.D., Ph.D., is evaluating a novel therapy for a unique genetic subset of thyroid cancer and Mark S. Cohen, M.D. is translating natural product compounds called withanolides into novel therapies for endocrine malignancies. Research from the Hammer lab led to a spin-off company, Atterocor, that is moving forward translational research on a

medicine. The adrenal cancer project, under the leadership of Giordano and Hammer, is nearing completion.

“As we learn more about genetics and genomics of endocrine cancers, we have an opportunity to incorporate targeted therapies to attack these mutations, as evidenced by the recent availability of novel targeted therapies for thyroid cancer and the NETs,” says Hammer. “Results from Phase 1, 2 and 3 studies are forthcoming which we hope will continue to expand and refine treatment regimens that enhance quality and prolong the life of unique genetic subsets of our patients.”

For more about the Endocrine Oncology Program, visit mcancer.org/endocrine-cancer or call M-LINE at 800-962-3555 for a consult or referral with one of the endocrine oncology specialists.

From Humble Beginnings to Major Progress in Rare Tumors

Gary D. Hammer, M.D., Ph.D.

Page 3: Update January 2015

subspecialty,

M-LINE I 800-962-3555 I mcancer.org

Higher Standards Needed Around Tumor Biomarkers

As more potential tumor biomarkers are identified to help diagnose cancer and determine treatment, it becomes increasingly important to

ensure that these markers are reliable and relevant.

Researchers at the University of Michigan Comprehensive Cancer Center urge more rigorous evaluation of tumor biomarkers. Daniel F. Hayes, M.D., clinical director of the breast oncology program and newly elected president of the American Society of Clinical Oncology, explains.

You have referred to tumor biomarkers as caught in a “vicious cycle.” What do you mean by that?

Hayes: Biomarkers are not valued nearly to the extent that we see with therapeutics. Regulatory rules are inconsistent, third-party payment is inadequate and tumor biomarker research is underfunded. All this

combines to create a vicious cycle that prevents development and testing of reliable biomarker tests that could be used to personalize clinical care of patients with cancer.

If a tumor biomarker test is used to decide whether a patient should receive a certain treatment, then it is as critical for patient care as a therapeutic agent. A bad biomarker test is as dangerous as a bad drug.

What makes a biomarker test good?

Hayes: First, a biomarker test must have analytical validity. We need to know it is accurate, precise, reliable and reproducible. In addition, it must have clinical validity. A biomarker needs to divide a population into two or more groups based on differences in biology or a certain clinical outcome. Clinical validity also means that we need high levels of evidence that when used to determine treatment, a biomarker test improves the patient’s outcome or delivers equivalent care at a lower cost.

What do you recommend?

Hayes: My colleagues and I have made several transformative

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recommendations to break the vicious cycle:

1. Reform regulatory review of tumor biomarker tests

2. Increase reimbursement for tumor biomarker tests that are proven to help determine which therapies will or are working

3. Increase investment for tumor biomarker research so it is comparable to new drug research

4. Increase the rigor for peer review of tumor biomarker publications

5. Include only proven biomarker tests in evidence-based care guidelines

These recommendations are not about creating more regulation; they are about creating an even playing field that allows tumor biomarker tests to be developed and proven clinically relevant. We want to stimulate innovation yet hold investigators and clinicians to the highest scientific standards – as we now do for therapeutics. We need to change the way we value tumor biomarkers in this country.

Daniel F. Hayes, M.D.

Page 4: Update January 2015

Executive Officers of the University of Michigan Health SystemMichael M.E. Johns, M.D., Interim Executive Vice President for Medical Affairs; James O. Woolliscroft, M.D., Dean, U-M Medical School; T. Anthony Denton, J.D., MHA, Acting Chief Executive Officer, U-M Hospitals and Health Centers; Kathleen Potempa, Ph.D., Dean, School of Nursing.

The Regents of the University of MichiganMark J. Bernstein, Julia Donovan Darlow, Laurence B. Deitch, Shauna Ryder Diggs, Denise Ilitch, Andrea Fischer Newman, Andrew C. Richner, Katherine E. White, Mark S. Schlissel, ex officio.

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Continued from page one

receptor that makes breast cancer resistant to aromatase inhibitors – and rare tumors – a gene fusion in solitary fibrous tumor.

“Genetic sequencing is extremely important with rare tumors,” Chinnaiyan says. “Models of rare cancers to study in the laboratory are either not available or very limited. The sequencing helps us to learn more about the disease that we can use to develop better treatments or to help diagnose the cancer in others.”

Through informed consent, patients with metastatic or refractory cancer for whom standard therapies are not

MI-ONCOSEQ Gene Sequencing Program

Precision Medicine Tumor Board

effective can be evaluated. For more information or to refer a patient, call M-LINE at 800-962-3555.