Jeff Settleman

Jeff Settleman discovered drug tolerant persister (DTP) cells in cancer, demonstrating that a subpopulation of cancer cells can survive lethal drug exposure through reversible epigenetic changes rather than genetic mutations, fundamentally challenging the mutation-centric view of drug resistance. His laboratory showed that DTP cells enter a quiescent state mediated by chromatin remodeling involving KDM5A histone demethylase and IGF-1R signaling. He established that DTP cells serve as a reservoir from which genetically resistant clones eventually emerge, making persister cell elimination a strategy to prevent acquired resistance. His discovery has opened the field of non-genetic drug resistance in cancer.