Dissecting Therapeutic Resistance to RAF Inhibition in Melanoma by Tumor Genomic Profiling

A detailed understanding of the mechanisms by which tumors acquire resistance to targeted anticancer agents should speed the development of treatment strategies with lasting clinical efficacy. RAF inhibition in BRAF-mutant melanoma exemplifies the promise and challenge of many targeted drugs; although response rates are high, resistance invariably develops. Here, we articulate overarching principles of resistance to kinase inhibitors, as well as a translational approach to characterize resistance in the clinical setting through tumor mutation profiling. As a proof of principle, we performed targeted, massively parallel sequencing of 138 cancer genes in a tumor obtained from a patient with melanoma who…

• MR
  Melanoma Research Alliance
• AS
  American Society of Clinical Oncology
• NI
  National Institutes of Health

  Award: U24CA143867
• NI
  Novartis Institutes for BioMedical Research
• FM
  Foundation Medicine
• NC
  National Cancer Institute