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Robert A. Weinberg, PhD
Member, Whitehead Institute
Director, Ludwig Center for Molecular Oncology
Massachusetts Institute of Technology
Goal: To understand why aggressive breast cancers are resistant to current treatments
Impact: Metastatic breast cancer is an aggressive disease and commonly resistant to multiple therapies. Dr. Weinberg is conducting a series of studies to identify new targets for prevention and treatment of metastatic breast cancer.
What’s next: He and his team will focus on cells derived from bone marrow that may help aggressive cancers evade immune attack. In addition, they plan to examine how breast cancer cells convert into cancer stem cells, the cells that drive metastasis and drug resistance.
While immunotherapy has been effective in improving survival rates of several types of the cancer, breast cancer patients do not respond as well to it. Dr. Weinberg is exploring how subsets of cells within breast tumors and metastatic lesions are able to evade immune attack, with a specific focus on cancer stem cells—the key drivers of tumor growth, drug resistance, and metastasis. These studies may pave the way for the development of new treatment options that will improve outcomes for patients with, or at risk of developing, metastatic breast cancer.
Full Research Summary
Research area: Determining the underlying biology leading to treatment resistance and metastasis of breast cancer.
Impact: In spite of the tremendous progress in breast cancer treatments, resistance to these therapies remains a serious clinical challenge and is the underlying reason for most diagnoses of metastatic breast cancer, cancer that has spread to other tissues. Dr. Weinberg’s BCRF research aims to understand the underlying biology that allows cancer cells to grow and survive attacks from the immune system, as well as current treatment strategies.
Current investigation: Dr. Weinberg is pursuing two lines of research: 1) elucidating the molecular mechanisms of resistance to immunotherapy, and 2) examining how cancer stem cells—a specialized population of cancer cells that are believed to be responsible for drug resistance and metastasis—are formed and how they persist within primary tumors.
What he’s learned so far: Dr. Weinberg and his colleagues have discovered that therapy-resistant cancer cells are able to recruit tumor-promoting immune cells that assist the tumor in evading immune surveillance. Understanding how these immunosuppressive cells are recruited to breast cancers will inform more effective immunotherapies for patients with aggressive breast cancers.
What’s next: He and his team will continue to investigate how cells from the immune system are recruited by breast tumor cells and hope to reveal targetable vulnerabilities in primary breast cancers that may enhance the effectiveness of immunotherapy approaches. In other studies, Dr. Weinberg will examine the characteristics of cancer stem cells that mediate their intrinsic resistance to current chemo- and immunotherapies, resulting in the metastatic spread of breast cancer cells from primary tumors to distant sites in the body.
Dr. Weinberg is a founding member of the Whitehead Institute for Biomedical Research and the Daniel K. Ludwig Professor for Cancer Research at the Massachusetts Institute of Technology (MIT). He is also the first Director of the Ludwig Cancer Center at MIT. He is an internationally recognized authority on the genetic basis of human cancer. Dr. Weinberg and his colleagues isolated the first human cancer-causing gene, the ras oncogene, and the first known tumor suppressor gene, Rb, the retinoblastoma gene. Research in Dr. Weinberg's laboratory is focused on attempting to elucidate the biochemical and cell-biological mechanisms that enable carcinoma cells in primary tumors to invade and disseminate, resulting in the formation of metastases in distant sites. Much of this work depends on analyses of the cell-biological program termed the epithelial-mesenchymal transition (EMT). In addition to conferring traits such as motility and invasiveness on epithelial carcinoma cells, activation of this program heightens their resistance to chemotherapeutic attack. In recent years the Weinberg laboratory has also found that activation of a previously latent EMT program places both normal and neoplastic epithelial cells in a position from which they can enter into a stemcell state. In the case of carcinomas, the tumor-initiating powers resulting from this shift indicates the formation of cancer stem cells (CSCs), which are qualified to serve as founders of new metastatic colonies in distant anatomical sites. Dr. Weinberg's research has increasingly focused on the interaction of CSCs with recruited inflammatory cells and on the later steps of the invasion-metastasis cascade that enables disseminated carcinoma cells to extravasate, thereby setting the stage for the formation of micro- and macroscopic metastatic colonies.