Deep and lasting response and acquired resistance to BRAFV600E targeting in a low-grade ovarian cancer patient

Cancer Biol Ther. 2023 Dec 31;24(1):2193116. doi: 10.1080/15384047.2023.2193116.

Abstract

The treatment of BRAFV600E mutant melanoma has been revolutionized by BRAF inhibitors. Furthermore, the BRAF/MEK combination has shown further improvement in clinical outcomes in advanced and in adjuvant melanoma patients. In low-grade ovarian tumors, BRAF inhibitor use has been also proposed. Here we present a patient with an excellent, lasting response to BRAF therapy alone. At first progression, after more than two years on BRAF monotherapy, we could not identify any molecular mechanisms explaining resistance. After a switch to dual BRAF/MEK therapy, the patient responded. However, despite the initial response clinical the patient again progressed, this time with the appearance of a KRAS G12C mutation, which could not be overcome by BRAF/MEK therapy. We provide evidence that BRAF inhibitor alone can be highly beneficial in BRAF mutant low-grade ovarian tumors and the resistance mechanisms are similar to that of other BRAF mutant tumors, including in melanoma.

Keywords: BRAF; Ovarian cancer; adaptation; resistance.

Publication types

  • Case Reports

MeSH terms

  • Female
  • Humans
  • Melanoma* / drug therapy
  • Melanoma* / genetics
  • Melanoma* / pathology
  • Mitogen-Activated Protein Kinase Kinases
  • Mutation
  • Ovarian Neoplasms* / drug therapy
  • Ovarian Neoplasms* / genetics
  • Protein Kinase Inhibitors / pharmacology
  • Protein Kinase Inhibitors / therapeutic use
  • Proto-Oncogene Proteins B-raf / genetics

Substances

  • Proto-Oncogene Proteins B-raf
  • Protein Kinase Inhibitors
  • Mitogen-Activated Protein Kinase Kinases

Grants and funding

The author(s) reported there is no funding associated with the work featured in this article.