Identifying Epigenetic Modulators of Resistance to ERK Signaling Inhibitors
Annual rept. 1 Aug 2014-31 Jul 2015
ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI NEW YORK
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Recent studies uncovered a role for chromatin regulators in response to targeted therapies in cancer. However, a global and unbiased approach to decipher the epigenetic mechanisms underlying melanoma drug resistance has yet to be reported. Our studies are revealing an epigenomic map of drug resistant cells and will allow us to uncover key epigenetic regulators underlying ERK signaling inhibitor resistance of malignant melanoma. Since our current knowledge of the chromatin biology underlying the process of drug resistance to ERK signaling inhibitors is essentially nil, we are taking innovative high-throughput approaches to study this intriguing and critical issue. Our work over the past year has identified chromatin mediators that when depleted form cells, enhance the melanoma drug resistance phenotype. These are novel findings to our knowledge and implicate distinct mechanisms of chromatin regulation in this process. This approach is also highly clinically relevant, as it will provide rationale for combining therapy targeted against identified epigenetic modulators with current therapies.
- Genetic Engineering and Molecular Biology
- Anatomy and Physiology
- Medicine and Medical Research