Taran Gujral, Ph.D.
Fred Hutchinson Cancer Research Center
Funded in Partnership with the American Lung Association of the Mountain Pacific
Genetic Mutation Could Help Predict Response to Lung Cancer Chemotherapy
Serine/threonine kinase 11 (STK11) ranks among the most frequently mutated genes in lung cancer. However, there is no therapy approved that specifically targets this mutation. We have found that STK11 mutations play a role in response to the chemotherapy drug gemcitabine. The status of these mutations might be used to predict patients' response to treatment. We will validate the role of STK11 mutations in the response to gemcitabine in lung cancer cell lines and a STK11-deficient mouse model. We hope the findings will accelerate development of a therapeutic option for many lung cancer patients and establish STK11 mutations as predictive markers for response to chemotherapy, a finding which could have an immediate clinical utility.
Update: We have validated our findings that STK11 mutant lung cancer cell lines are sensitive to gemcitabine. We also carried out a comprehensive drug screen and discovered chemical compounds called DNA topoisomerase inhibitors and cell cycle inhibitors are also selectively effective on cells which mimic STK11 mutations. We are continuing to validate these findings in a STK11-deficient mouse model, and we are gaining molecular understanding of how STK11 mutations confer sensitivity to these drugs. Finally, we also made progress in testing our hypothesis that STK11 mutations can be used as a prognostic marker for lung cancer.