For people with lung cancer, drug resistance is the major cause of relapse. A tumor might respond very well at first — maybe even shrinking down to an undetectable level — only to develop resistance and grow back.
Scientists are learning that one of the ways that lung cancers become resistant is through something called lineage plasticity. This means that lung cancer cells are essentially changing their identity so they are no longer dependent on the chemical process that the drug was designed to target.
In the case of lung cancer that is fueled by abnormal activity of the epidermal growth factor receptor (EGFR), which often treated with the targeted drug osimertinib (Tagrisso®), that means switching to a type of growth that bypasses EGFR.
Cancer biologist Triparna Sen, an Assistant Attending Biologist in the Thoracic Oncology Service in the Department of Medicine at MSK, and her colleagues are focused on trying to understand the drivers of these identity changes so that they can develop more effective therapies for people with lung cancer.
“We think this lineage plasticity depends on cells turning on or off different genetic and epigenetic programs,” Dr. Sen says. “But the specific genes that drive a particular transformation from one type of lung cancer into another are just now coming to light.”