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Robert A. Weinberg, PhD

Member, Whitehead Institute
Director, Ludwig Center for Molecular Oncology
Massachusetts Institute of Technology
Cambridge, Massachusetts

Current Research

  • 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 stem cells (CSCs) are rare, highly specialized cells within a tumor. While they represent a small fraction of tumor cells, they are the key drivers of tumor growth, drug resistance and metastasis. Dr. Weinberg is conducting studies aimed at understanding how interactions of CSCs with other cells promote resistance to therapy and evasion of the immune system. 

Full Research Summary

Cancer cells have the unique ability to assume different characteristics that allow them 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.

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. His research in the next year will focus on two ongoing areas of study: 

  1. Understanding how subsets of cells within primary and metastatic breast cancers escape attack and elimination by the immune system: In previous work, Dr. Weinberg’s group discovered that therapy-resistant cancer cells are able to recruit "immunosuppressive" cells. These cells originate in the bone marrow and migrate to breast tumors, where they thwart attacks on breast cancers by the immune system.  His group will examine precisely how such immunosuppressive cells are recruited to breast cancers to uncover possible vulnerabilities in primary breast cancers that can be interrupted, thereby allowing effective immune attack on these tumors.
     
  2. Examining the internal regulatory circuitry of individual cancer stem cells (CSCs) within primary breast tumors to understand how these cells resist various types of therapies and spread to distant sites in the body: The CSCs within breast tumors exhibit multiple traits that render them resistant to various types of therapy. Dr. Weinberg’s recent studies revealed the identities of several proteins in the nucleus of CSCs that operate as master regulators of cell behavior. His group will continue these studies to understand how these proteins orchestrate the malignant growth program of these cells. 

These exploratory studies are critical in informing new treatment options and guiding the development of more effective drugs.

Biography

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.

 

BCRF Investigator Since

2003

Donor Recognition

The Lampert Foundation Award

Area(s) of Focus