Targeting Cellular Plasticity in Individual Basal-type Breast Cancer Cells
Targeting Cellular Plasticity in Individual Basal-type Breast Cancer Cells
Investigator
John G. Albeck, PhD
Assistant Professor, Department of Molecular and Cellular Biology
University of California, Davis
Davis, California
Summary
Healthy cells lack the ability to survive outside their original niche, but during cancer progression, malignant cells acquire the ability to adapt to foreign environments. This property of adaptability, which is referred to as “plasticity,” is possible because tumor cells are able to reconfigure their genetics to better fit the new niche they find when they spread to different organs. A similar adaptation process can occur when tumor cells are treated with drugs; although at first the drug may work against the tumor, internal processes in the cancer cells change to make them more resistant to therapy. The goal of this project is to better understand the fundamental internal processes of plasticity in cancer cells, so that we can find better ways to defeat metastases and drug-resistance.
While it is unclear how tumor cells perform the internal reconfigurations needed for adaptation, it is known that biochemical pathways that specialize in transmitting messages within the cell and controlling gene expression are involved. The Albeck lab has developed an imaging technique that allows these messaging pathways to be monitored continuously in living cells, providing a new window into how cells decide which genes to turn on or off. The hypothesis is that random periods of gene activity intensify as the cellular environment changes during tumor progression, allowing some tumor cells to activate genetic programs that provide them with a survival advantage. This hypothesis will be tested by combining the novel imaging technology with a cell culture system that mimics different points in a tumor’s progression. Cellular survival in response to chemotherapy will be tracked, as well as the random changes that provide cells with temporary resistance to drugs. By tracking the underlying diversity of evolving tumor cell populations and focusing on the most drug-resistant cells, the hope is to identify new treatment strategies that are more effective and have fewer side effects.
Updated: May 2016