Member, Whitehead Institute
Director, Ludwig Center for Molecular Oncology
Massachusetts Institute of Technology
Seeking to understand the interaction of cancer stem cells with other cells in the tumor environment
Laboratory studies are focused on understanding the complex nature of cancer stem cells to identify targets for more effective therapies for aggressive breast cancers.
These studies will greatly advance our understanding of tumor biology and inform new strategies to improve outcomes in breast cancer patients with advanced disease.
Cancer cells have the unique ability to assume different characteristics that make them more or less able to invade tissue and seed new tumors at distant sites, a process called metastasis. The more dangerous of these cells are the cancer stem cells, which serve as the founders, or origins, of new metastatic colonies.
Normal stem cells can be converted to cancer stem cells, but scientists don't fully understand this process or what conditions are required. The goal of Dr. Weinberg's project is to decipher the interaction of stem cells and cancer cells and how this leads to cancer development and progression.
Several lines of research are planned: 1) Develop new biochemical markers for identifying and purifying cancer stem cells; 2) determine how many distinct subtypes of breast cancer cells co-exist within a single tumor and whether these subtypes inter-convert with one another; 3) understand the mechanisms by which stem cell and related cancer cells avoid attack by the immune system and resist immune-targeted therapies.
These exploratory studies are critical in informing new treatment options and guiding the development of more effective drugs.
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.