Sridhar Ramaswamy, MD, Tucker Gosnell Investigator and Associate Professor of Medicine, Massachusetts General Hospital Cancer Center, Harvard Medical School, Broad Institute of Harvard & MIT, and Harvard Stem Cell Institute, explains that every tumor, no matter what type, displays a certain degree of heterogeneity.

Heterogeneous cells can vary on both a molecular and genetic basis. Some cells differentiate on a cellular level by displaying various patches on the cell surface that are different than the rest of the cell. Cellular disparity may contribute to tumor recurrence and therapy resistance.

When examining the cells, different classifications arise. Some are pre-apoptotic and are near the point of programmed cell death; this type will not cause issues in the future. Other cells are senescent, which do not proliferate. The most interesting set are the sleeping or dormant cells, which can be implicated in drug tolerance. Sleeping cells are particularly interesting because of their ability to move in and out of the dormant state.

Ramaswamy notes that understanding the mechanism of heterogeneity may help understand the dynamics of tumor growth, which could lead to a more sustainable drug response.

Videos

Dr. Sridhar Ramaswamy from the Massachusetts General Hospital Cancer Center Discusses Tumor Heterogeneity

Dr. Ramaswamy Discusses Tumor Heterogeneity

Sridhar Ramaswamy, MD, Tucker Gosnell Investigator and Associate Professor of Medicine, Massachusetts General Hospital Cancer Center, Harvard Medical School, Broad Institute of Harvard & MIT, and Harvard Stem Cell Institute, discusses ongoing research into drug tolerance and resistance, specifically the roll of dormant cancer cells.

If a tumor goes into remission as a result of a cancer drug and then recurs it is likely that the tumor will still respond to the initial treatment. In the dormant state the cells are resistance, in the original they are sensitive. The exact mechanism behind this has yet to be discovered. In some cases giving a course, stopping, and then continuing later on can create an additive effect, an idea that Ramaswamy calls a drug holiday.

A comparison is underway between drug and non-drug induced dormant cells in order to find the mechanism that causes resistance. The ultimate goal of the research is to be able to predict and stop drug resistance.

Dr. Sridhar Ramaswamy, from Massachusetts General Hospital Cancer Center, on Dormant Tumor Cells and Resistance

Dr. Ramaswamy on Dormant Tumor Cells and Resistance

Sridhar Ramaswamy, MD, Tucker Gosnell Investigator and Associate Professor of Medicine, Massachusetts General Hospital Cancer Center, Harvard Medical School, Broad Institute of Harvard & MIT, and Harvard Stem Cell Institute, discusses targeting dormant cancer cells and the possible role that they play in the development of drug resistance.

Dormant cells appear in most patients with tumors. These cells are not rapidly proliferating and remain largely inactive. While these cells sleep, they are highly resistant to most types of therapy.

Dormant cancer cells are intrinsically intriguing because the number of inherent mutations would denote that the cells should be rapidly proliferating. The mechanism that allows them to switch between dormant and active is yet unknown. The goal of the research is to discover the underlying cause of the dormancy, tumor progression, and the mechanism of resistance to various types of therapy.

Dr. Sridhar Ramaswamy, from Massachusetts General Hospital Cancer Center, on Targeting Dormant Cancer Cells

Sridhar Ramaswamy, MD

Articles

Dr. Ramaswamy Discusses Tumor Heterogeneity

Dr. Ramaswamy on Dormant Tumor Cells and Resistance

Dr. Ramaswamy on Targeting Dormant Cancer Cells