Healthy cells are unable to survive outside their original niche, but during cancer progression, malignant cells acquire the ability to adapt to foreign environments. This property of adaptability, or “plasticity,” is possible because tumors are able to change over time 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 onto 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 give them a survival advantage. Albeck is testing this hypothesis by combining his lab’s 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 will 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 researchers hope to identify new treatment strategies that are more effective and have fewer side effects.