Nongenetic Mechanisms of Drug Resistance in Melanoma

Vito W. Rebecca, Meenhard Herlyn

Research output: Contribution to journalReview articlepeer-review


Resistance to targeted and immune-based therapies limits cures in patients with metastatic melanoma. A growing number of reports have identified nongenetic primary resistance mechanisms including intrinsic microenvironment- and lineage plasticity-mediated processes serving critical functions in the persistence of disease throughout therapy. There is a temporally shifting spectrum of cellular identities fluidly occupied by therapy-persisting melanoma cells responsible for driving therapeutic resistance and metastasis. The key epigenetic, metabolic, and phenotypic reprogramming events requisite for the manifestation and maintenance of so-called persister melanoma populations remain poorly understood and underscore the need to comprehensively investigate actionable vulnerabilities. Here we attempt to integrate the field's observations on nongenetic mechanisms of drug resistance in melanoma. We postulate that the future design of therapeutic strategies specifically addressing therapy-persisting subpopulations of melanoma will improve the curative potential of therapy for patients with metastatic disease.

Original languageEnglish (US)
Pages (from-to)315-330
Number of pages16
JournalAnnual Review of Cancer Biology
StatePublished - Mar 4 2020
Externally publishedYes


  • neural crest stem cell, plasticity, dedifferentiation, therapy resistance, metastasis

ASJC Scopus subject areas

  • Cancer Research
  • Cell Biology
  • Oncology


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