FAK Signaling and Chemotherapy Resistance in Ovarian Cancer
Posted: Friday, September 27, 2019
A new research study, published in eLife and conducted by co-principal investigator Dwayne G. Stupack, PhD, of Moores Cancer Center, San Diego, and colleagues, found that later-stage, more aggressive ovarian cancer cells had a genetic change in the FAK protein—it had more copies than normal. When these cells grew as tumorspheres, the tumors became more resistant to chemotherapy than the early-stage cancer cells.
“We have linked elevated levels of FAK, or gene amplification, to the survival of cancer stem cells in a new tumor model. We knew FAK helped tumors to spread, but we were surprised to find that FAK supports DNA repair in the most important stem-like cells of the tumor,” stated co-principal investigator David D. Schlaepfer, PhD, of the UC San Diego School of Medicine, in a UC San Diego News Center press release.
For the study, the researchers evaluated early- and late-stage ovarian cancer cells that were grown in mice. The cancer cells that were resistant to chemotherapy shrunk when combined with a drug targeting the FAK enzyme. It was also found that FAK proteins activated a group of genes that increased the resistance to chemotherapy and repaired damaged DNA.
In closing, Dr. Stupack offered his perspective on the clinical implications of their study findings. “When we treated mice that had chemoresistant tumors with a FAK inhibitor, they responded to chemotherapy. Mice that did not receive the FAK inhibitor were resistant. By understanding the biology behind this, it can help us prepare better combinations of drugs for the clinic.”
Disclosure: The authors’ disclosure information can be found at elifesciences.org.