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5th World Congress on Cancer Therapy

Atlanta, USA

Raffaella Sordella

Cold Spring Harbor Laboratory, USA

Title: Cancer cell- state plasticity and resistance to therapy


Biography: Raffaella Sordella


Therapeutic resistance has been proven to be one of the foremost obstacles limiting the clinical effi cacy of cancer drug treatments including targeted therapies for non-small cell lung cancers (NSCLC) harboring activating EGFR mutations. Recent evidence indicated that the intrinsic heterogeneity of tumors is one of the main mechanisms of acquired drug resistance. Here we show that NSCLC harboring EGFR mutations can become resistant to inhibition of EGFR via a novel epigenetic mechanism. By modeling erlotinib resistance, we identifi ed a drug-tolerant cell population that is already present in NSCLC populations prior to drug treatment. Th ese erlotinib-resistant cells are regulated epigenetically and represent an alternative cell state in which cancer cells can reside in. Th e transition between these diff erent cell states modifi es the cell signaling network, reworks cancer cell dependency and induces a hypermutable phenotype. Th ese fi ndings provide a rationale for incorporating novel fi rst-line combination therapies in the treatment of NSCLC harboring EGFR-activating mutations.