The goals of the Department of Medical Oncology are to provide expert care to all adult patients with cancer, and to conduct cutting edge laboratory and clinical research that will the improve the diagnosis and treatment of all types of cancers.
Overview of the Department
The Department of Medical Oncology is committed to offering compassionate care to adult patients with cancer, cutting-edge clinical and basic research, and outstanding training opportunities for basic and clinical investigators. More than 225 faculty members are organized into fourteen multidisciplinary disease centers and three research divisions.
Each of the fourteen disease centers is focused on a specific type of cancer, and is directed by a nationally recognized leader who is responsible for the clinical and research activities of their center. These include:
- Bone and Sarcoma Oncology (George Demetri, MD)
- Breast Oncology (Eric P. Winer, MD)
- Cancer Genetics (Judy Garber, MD)
- Carole M. and Philip L. Lowe Center for Thoracic Oncology (Pasi Jänne, MD, PhD)
- Early Drug Development Center (Geoffrey Shapiro, MD, PhD)
- Melanoma (Stephen Hodi, MD)
- Gastrointestinal Oncology (Brian Wolpin, MD, MPH)
- Gynecological Malignancies (Ursula Matulonis, MD)
- Head and Neck Oncology (Robert Haddad, MD)
- Hematologic Oncology (Robert Soiffer, MD)
- Lank Center for Genitourinary Oncology (Toni Choueiri, MD)
- Neuro-Oncology (Patrick Wen, MBBS)
In addition, Medical Oncology works closely with two additional disease centers located primarily at the Brigham and Women’s Hospital:
These centers are also responsible for teaching and mentoring of the 14 first-year clinical medical oncology fellows at Dana-Farber/Partners CancerCare, as well as many senior fellows, under the overall supervision of Dr. Ann LaCasce, the Director of the Medical Oncology/Hematology Training Program. Clinical care and clinical research are highly coordinated with other Dana-Farber clinical and research departments.
There are approximately 45 independent research laboratories in the Department, divided into three research divisions:
- Molecular and Cellular Oncology (William Hahn, MD, PhD)
- Hematologic Neoplasia (Margaret Shipp, MD)
- Population Sciences (Deborah Schrag, MD)
A major departmental research theme is linking knowledge of the genes that cause cancer to the discovery and testing of new therapeutics, involving both small-molecule drugs and immune approaches. Other key themes relate to developing personalized medicine strategies by using genetic, epidemiologic, immunologic, and population-based studies to determine risk and ideal treatment for individual patients.
Clinical Research Accomplishments
Some of the major accomplishments in the department’s clinical research over the last five years include:
- The successful funding or re-funding of multiple translational program project grants and SPORES in acute lymphoblastic leukemia, acute myeloid leukemia, chronic lymphocytic leukemia, lymphoma, myeloma, prostate cancer, renal cancer, lung cancer, breast cancer, pancreatic cancer, glioblastoma, cutaneous oncology, and allogenic hematopoietic stem cell transplantation. Numerous grants to support sequencing and analysis of human tumor specimens have also been funded.
- The opening of approximately 150 new therapeutic clinical research trials in oncology each year, accruing of more than several thousand patients annually onto therapeutic trials.
- The success of the expanded outpatient clinical research center in the Yawkey Center for Cancer Care, with multiple infusion beds dedicated to patients being treated in high-intensity Phase I therapeutic clinical trials.
- Development and implementation of a training program for clinical investigators, specifically targeted at the junior faculty and senior fellow stages, and improved infrastructure to support clinical trial research. A training program for clinical investigators interested in immunotherapy trials is in development.
- Development of rapid genotyping tests for solid and liquid tumors, focusing on actionable mutations. These tests identify all known actionable mutations in each person’s tumor, and can be used to personalize treatment options. The results of the Rapid Heme Panel (for patients with leukemias and lymphomas) are available to patients in about four days, and this test has transformed decision-making in many types of hematologic malignancies.
- The opening of a novel Immuno-Oncology Center led by Stephen Hodi, MD, which coordinates clinical trials involving immunotherapy agents, such as checkpoint inhibitors CLTA-4 and PD-L1, as well as a growing number of novel immunomodulatory drugs in clinical trials. The center has led a number of immunotherapy trials with high impact, and these results have collectively led to new standard treatments for patients with melanoma, non-small cell lung cancer, and subsets of patients with Hodgkin’s disease, renal cell cancers, and others.
Advances in Clinical Research
There have been major advances in the care of cancer patients over the last decade, resulting in a significant decline in cancer death rates of the last few years. Members of the Department of Medical Oncology have contributed significantly to these advances through clinical trial activities. Some of the recent advances include:
- Discovery that the state of mitochondrial priming for apoptosis can be used as a predictive test for sensitivity to chemotherapy in acute myeloid leukemia (AML), in particular (Anthony Letai, MD, PhD), and the development of clinical trials testing anti-BCL2 drugs and other BH3 mimetics with impressive clinical results.
- Multiple clinical studies showing the remarkable potential of anti-PD-1 and anti-PD-L1 antibodies for immunotherapy of patients with cancer (Stephen Hodi, MD) PD-L1 was discovered by division member Gordon Freeman, PhD, along with Arlene Sharp at HMS.
- Discovery of high rates of complete responses in patients with relapsed Hodgkin’s lymphoma with anti-PD-LI (Philippe Armand, MD, PhD, and Margaret Shipp, MD).
- Important advances in our uses of the immunotherapeutic ipilumimab in combination with anti-PD-1 therapy, resulting in a higher number of responses, and longer duration of responses, without significant increases in toxicity.
- Further development of highly effective combination therapy for myeloma involving imides drugs, and bortezomib (Kenneth Anderson, MD, and Paul Richardson, MD), with numerous studies currently testing new generations of proteasome inhibitors, HDAC inhibitors, and immune therapies.
- The discovery of new cellular and microenvironmental immunotherapy targets.
- The development and testing of new cancer vaccine strategies, particularly in the areas of antigen presentation and adjuvants.
- Advances in the adjuvant treatment of small, HER2-positive breast cancers with paclitaxel and traztuzumab (Sarah Tolaney, MD, and Eric Winer, MD).
- Advances in the pathogenesis and systemic chemotherapy of neuroendocrine tumors (Matthew Kulke, MD).
- Multiple studies on the mechanisms of resistance to ALK and EFGR inhibitors in lung cancer and strategies to avert and bypass resistance mechanisms (Pasi Jänne, MD, PhD, Bruce Johnson, MD, and others).
- The development of successful new small-molecule drugs for chronic lymphocytic leukemia (CLL) (Jennifer Brown, MD, PhD, Matthew Davids, MD, and Catherine Wu, MD).
- The development of small molecule inhibitors of FLT3, a kinase mutated in about one-third of patients with AML, leading to clinical trials showing prolongation of survival of these patients.
Advances in Basic Research
During the last few years, basic research in the division has expanded considerably through recruitment. Although there is a wide variety of research conducted in the department, a particular focus has been on discovering the genetic events that lead to different cancers. Recent studies in head and neck cancer, neuroendocrine tumors, lung cancer, glioblastoma, Waldenström’s Macroglobulinemia, CLL, lymphoma, papillary and anaplastic thyroid cancer, and renal cancer have been particularly informative. Some notable discoveries include:
- Discovery of HIF2a inhibitors and demonstration of preclinical activity (William Kaelin, MD)
- Pangenomic characterization of adrenocortical carcinoma, uterine carcinosarcomas, paragangliomas, pheochromocytomas, cervical cancer, lung cancers, gliomas, gastric cancers and many others (Matthew Meyerson, MD, PhD, and others).
- Discovery of DNA repair gene mutations in a subset of men with prostate cancers (Mark Pomerantz, MD, Matthew Freedman, MD, Levi Garraway, MD, PhD, and others).
- Studies on subclonal evolution and role of splicing factor mutations in CLL (Catherine Wu, MD)
- Discovery of mutation in MYD88 as the cause of Waldenstrom’s Macroglobulinemia and development of the BTK inhibitor ibrutinib as a highly effective therapy for this disease (Steven Treon, MD, PhD).
- Studies with genetically engineered mouse models (GEMM) of lung cancer, identifying multiple new therapeutic strategies, including CDK7 inhibitors (Kwok Wong, Md, PhD, Pasi Jänne, MD, PhD, and others).
- Demonstration of extensive reprogramming of the androgen receptor cistrome in prostate cancer (Matthew Freedman, MD).
- Multiple studies documenting the role of defects epigenetic regulation in the pathogenesis of cancers. (Myles Brown, MD).
- The discovery of small molecules that can target bromodomain proteins such as BRD4, leading to preclinical clinical trials showing efficacy of such agents in a variety of tumor types. (Jay Bradner, MD)
- Discoveries of several strategies to analyze tumors through circulating DNA or circulating tumor cells (Pasi Jänne, MD, PhD)
- Discovery of the mechanism of action of imide drugs such as lenalidomide in myeloma-- promoting the cereblon-dependent destruction of Ikaros proteins (William Kaelin, MD).
- Discovery of the mechanism of action of the IDH (isocitrate dehydrogenase) oncogenes. (William Kaelin and Julie Losman)