Revolutionary Research on Drug-Resistant Lung Cancer Genes

Cancer cells generate extra copies of genes called amplifications, which can promote their growth and survival. Johnathan Whetstine, Ph.D., Cancer Epigenetics Program Leader at Fox Chase Cancer Center and recipient of the American Lung Association’s Lung Cancer Discovery Award in 2014, 2017 and 2019, and his group of researchers believe that we can make strides in fighting this complicated disease by understanding how these cancer cells selectively amplify regions of the DNA to help them survive and resist therapy.

Dr. Whetstine

“It’s much easier to target a problem or fix it if you know what it is. The cancer cell is no different,” Dr. Whetstine explained. “Epigenetics, the study of how modifications to DNA and their surrounding environments affect our genes, is crucial in understanding the process responsible for controlling how DNA is amplified and selected so cancer gets a benefit. If we can understand this process, we can be more systematic in our drug design and predictions in controlling these events and the responses to therapies.”

Dr. Whetstine’s lab was the first to document the epigenetic modifiers and their related chemical modifications that promote DNA amplification of regions responsible for drug resistance. They began by exploring relationships in lung cancer and the process by which genes driving lung cancer were being amplified and impacting drug responses. Most recently, they uncovered the epigenetic regulators involved in controlling a well-known lung cancer oncogene called the epidermal growth factor receptor (EGFR). Details were published on November 27, 2019 in Cancer Discovery, a journal by the American Association for Cancer Research.  

“We were able to use our insights to apply drugs targeting the epigenetic factors to control EGFR amplification and response to chemotherapy. These results showed the world that we can use drugs to control DNA amplification and drug response,” said Dr. Whetstine. “Additionally, the researchers realized that epigenetic regulators could act as biomarkers to make predictions to drug response or lack thereof.” 

What is truly exciting is that these findings can guide us to map additional insights into the constantly changing lung cancer cells, as well as guide our understanding about DNA amplification events that are driving other cancers. The fundamental discoveries are positioned to cross cancer lines and allow for a dramatic impact. 

“The Lung Association’s commitment to discovery in order to advance treatment and understanding of lung cancer is one of the reasons we have made such progress,” Dr. Whetstine concluded. “They are committed to the science, in addition to the mission, to help lung cancer patients and families. They have helped us spread the word about these cutting-edge findings, so they know exciting findings are happening and breakthroughs are on the horizon. We’re excited to explore these possibilities ahead with our clinical collaborators.” 

Page last updated: January 20, 2021

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