Johnathan Whetstine, Ph.D.
Massachusetts General Hospital
Funded by the American Lung Association of the Northeast
Identifying Genetic Factors Influencing Drug Resistance in Lung Cancer
Identifying factors and mechanisms influencing genetic mutations and drug resistance will improve our ability to treat lung cancer. The enzyme KDM4A, overexpressed (meaning there are too many KDM4A enzymes produced) in lung cancer, leads to more DNA copies of genes associated with drug resistance and increased potential for the spread of lung cancer. In addition, reduced oxygen levels in lung tumors promote an increase in the number of copies of drug-resistant genes, which depends on KDM4A. We will investigate the molecular basis for KDM4A modulation of these processes in lung cancer. Ultimately, this research will uncover novel biomarkers for the disease and identify unappreciated drug targets to control resistant and aggressive lung cancer.
Update: During the past year, we have increased our collection of proteins in the cell that are able to increase the DNA content at sites that harbor genes that protect lung cancer cells from chemotherapy. These discoveries are included in a manuscript that is accepted to be published in a world-leading journal. These studies have also allowed us to begin investigations into possible drug design and applications for our findings.