Melanoma targeted therapies beyond braf-mutant melanoma: Potential druggable mutations and novel treatment approaches

Karam Khaddour, Lucas Maahs, Ana Maria Avila-Rodriguez, Yazan Maamar, Sami Samaan, George Ansstas

Research output: Contribution to journalReview articlepeer-review

3 Scopus citations


Melanomas exhibit the highest rate of somatic mutations among all different types of cancers (with the exception of BCC and SCC). The accumulation of a multimode of mutations in the driver oncogenes are responsible for the proliferative, invasive, and aggressive nature of melanomas. High-resolution and high-throughput technology has led to the identification of distinct mutational signatures and their downstream alterations in several key pathways that contribute to melanomagenesis. This has enabled the development of individualized treatments by targeting specific molecular alterations that are vital for cancer cell survival, which has resulted in improved outcomes in several cancers, including melanomas. To date, BRAF and MEK inhibitors remain the only approved targeted therapy with a high level of evidence in BRAFV600E/K mutant melanomas. The lack of approved precision drugs in melanomas, relative to other cancers, despite harboring one of the highest rates of somatic mutations, advocates for further research to unveil effective therapeutics. In this review, we will discuss potential druggable mutations and the ongoing research of novel individualized treatment approaches targeting non-BRAF mutations in melanomas.

Original languageEnglish
Article number5847
Issue number22
StatePublished - Nov 1 2021


  • BRAF
  • DNA damage repair
  • Epigenetic
  • Ho-mologous recombination deficiency
  • MEK
  • Melanoma
  • Molecular alteration
  • NF1
  • NRAS
  • Precision oncology
  • Targeted therapy
  • Tumor suppressor gene


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