Cancer Stem Cell Program

Program Head: Gary Gilliland, MD, PhD

Goal: to identify cancer stem cells in tumors and characterize their distinctive features for the development of therapeutic strategies that selectively target cancer stem cells

Every year, in the U.S. alone, there will be 10 million people suffering from the forms of uncontrolled cell growth we collectively call cancer, and 600,000 of them will die. The vast majority of current cancer treatments use either radiation or chemotherapy to shrink tumors by killing cancer cells and, unfortunately, they are not nearly as target specific as they should be and cause debilitating side-effects by killing health cells along with the cancer cells.

It has become apparent that tumors contain cancer stem cells and this could finally explain why tumors may regenerate after treatment. So developing therapies to specifically target these cancer stem cells offers an exciting new plan of attack for combating cancer.

To respond to this need, a group of HSCI researchers established a Cancer Stem Cell Program, bringing together basic scientists and clinicians from across the Harvard community, each contributing their expertise in the endeavor to understand the biology of cancer stem cells - how they differ from other tumor cells and normal cells - and to develop novel therapeutic approaches based on these insights. Located primarily at the Brigham and Women's Hospital, Dana-Farber Cancer Institute, and the Massachusetts General Hospital, the members of this program work closely with cancer surgeons who provide them with tumor cells from patients undergoing surgery. This group of investigators will characterize cancer stem cells from various tumors and study their biology. Once they uncover the molecular mechanisms and signaling pathways of the tumor stem cells, the HSCI team will begin to translate their insights into therapeutic approaches.

To accomplish these goals, the program will:

Identify cancer stem cells and investigate biological properties
Researchers have already identified markers and cancer stem cells in three cancer types - leukemia, breast cancer, and tumors of the central nervous system. As a next step, this program is using several strategies to search for markers that will allow for identification and purification of cancer stem cells in a variety of other tumors. These research techniques include investigating when and where certain genes are expressed (expression arrays), what signals are communicated from the outside into a cell (signal transduction), and the structure and function of proteins associated with these cells (proteomic analysis). Once cancer stem cells have been identified, specific cancer models will be developed, and the relationship between cancer stem cells and their normal tissue counterparts will be studied.

Study the microenvironment of tumor cells
Tumor cells may not be the only culprit cell type in the formation of cancer. It was previously believed that supportive (stromal) cells were passive bystanders during tumor growth, but evidence now indicates that they may play a significant role in tumor development. Researchers are re-creating the stromal microenvironment of tissues in a test tube, allowing them to study interactions between cancer stem cells and stromal tissue cells and to find ways to disrupt this interaction specifically target cancer stem cells.

Design target cancer stem cells for therapy
Specifically targeting cancer stem cells may provide an efficient and safe method for treating cancers. This requires searching for specific molecules that will inhibit the stem cells' duplication and therefore the growth of the tumor.. The Cancer Stem Cell Program is using several high throughput screening techniques to identify such inhibitors in a variety of tumor tissues, such as RNAi, which stops the function of particular genes within cancer stem cells; retroviral transduction, which allows the integration of genes into a cell; and cDNA libraries, which aid in the identification of genes that maintain cancer stem cell duplication.

Operate a core facility
The Cancer Stem Cell Program has established a core facility that will enable procurement of patient tissue, identify cancer stem cells by generating novel markers, and manipulate these cells in different models. The data and reagents generated by this program will be available to members of the other Disease Programs through a website that will house the cancer stem cell repository, list of reagents, online data and tool sharing and updates.

Cancer Stem Cell Program Lead HSCI Principal Faculty Investigators