Research Project: Why Do Some Cancer Cells Persist Despite Treatment for EGFR Lung Cancer?
Lung Cancer Discovery Award
combination therapies experimental therapeutics
Many patients with non-small cell lung cancer with a mutation in the EGFR gene initially respond well to the treatment. However, almost all of these cancers progress on therapy, even with recently developed EGFR inhibitor drugs such as osimertinib. Delaying acquired tolerance to EGFR inhibitors would clearly improve patient outcomes. The reason for certain cancer cells being left behind (known as persister cells) when the majority of cancer cells die is unknown. Taking into account the variety of cell response to the drug, we recently used a new approach that allowed us to identify metabolic differences between persister cells. We will study these differences in relation to the main pathway regulating cell response to anti-cancer drugs. We will identify persister vulnerabilities and may find new targets for combination drug therapy.
We showed that many of the processes defining persister cells are regulated by the protein called pRB. In this grant, we used various lung cancer models to address the question whether pRB is critical during the initial steps of developing persistence, and which pRB function should be restored to stop drug resistance. A better understanding of such cell-surviving strategies will be helpful for designing new treatments.