Johnathan Whetstine, Ph.D.

Lung cancer is the leading cause of cancer-related deaths in the U.S. Aberrant duplication of the genome contributes to a diverse population of cancer cells within lung tumors and increases lung cancer-associated risk and drug resistance. Identifying factors and mechanisms influencing genome stability and drug resistance will impact our ability to treat lung cancer. We discovered multiple enzymes that lead to localized variations in the number of DNA copies in regions linked to drug-resistant lung cancer. We will investigate the molecular details that these enzymes are controlling in order to generate variations in the number of copies of a particular gene, while establishing the impact that additional biological pathways have on cancer gene amplification (copies) in lung cancer. Our research will uncover novel biomarkers in lung cancer and identify unappreciated drug targets to control tumor diversity and resistant lung cancer. 

Previously funded

Institution: Fox Chase Cancer Center
Project: Enzyme Could Help Predict Effectiveness of Lung Cancer Chemotherapy
Grant(s): Lung Cancer Discovery Award

Abnormal gene expression and mutations contribute to lung cancer risk and drug resistance. The enzyme KDM4A, which is over-produced in lung cancer, leads to genetic changes which have been linked to drug resistance. The overproduction of KDM4A in cancer cells results in reduced response to drug treatment and radiation. We will study how KDM4A works in lung cancer cells, and whether levels of the enzyme are an important predictor of the effectiveness of chemotherapy against lung cancer.

Update:

Abnormal DNA duplication contributes to lung tumor variability and increases cancer-associated risk and drug resistance. Our laboratory is determining how extra copies/amplification of genes impacting lung cancer drug response are being generated. We also aim to control these amplification events and the associated therapeutic response. These data will identify novel drug targets for treating DNA amplification and drug resistance. In the past year, we identified factors targeting major lung cancer amplification events and demonstrated that we can therapeutically control DNA copy number in lung cancer cells. This set of discoveries was recently published. We also established additional pathways impacting lung cancer cells that we are exploring in the years ahead.