Identifying Epigenetic Modulators of Resistance to ERK Signaling Inhibitors

Abstract

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.

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Document Details

Document Type
Technical Report
Publication Date
Aug 01, 2015
Accession Number
ADA622203

Entities

People

  • Emily Bernstein

Organizations

  • Icahn School of Medicine at Mount Sinai

Tags

DTIC Thesaurus Topics

  • Biology
  • Cell Line
  • Cells
  • Chromosome Structures
  • Drug Resistance
  • Gene Expression
  • Genes
  • Genetics
  • Genome
  • Inhibitors
  • Medical Personnel
  • Melanoma
  • Modulators
  • Neoplasms
  • Regulators
  • Resistance
  • Throughput

Fields of Study

  • Biology

Readers

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  • Molecular and genetic basis of cancer.