Deep and lasting response and acquired resistance to BRAFV600E targeting in a low-grade ovarian cancer patient.
Details
Serval ID
serval:BIB_365141E36CC9
Type
Article: article from journal or magazin.
Publication sub-type
Case report (case report): feedback on an observation with a short commentary.
Collection
Publications
Institution
Title
Deep and lasting response and acquired resistance to BRAFV600E targeting in a low-grade ovarian cancer patient.
Journal
Cancer biology & therapy
ISSN
1555-8576 (Electronic)
ISSN-L
1538-4047
Publication state
Published
Issued date
31/12/2023
Peer-reviewed
Oui
Volume
24
Number
1
Pages
2193116
Language
english
Notes
Publication types: Case Reports ; Journal Article
Publication Status: ppublish
Publication Status: ppublish
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
Humans, Female, Proto-Oncogene Proteins B-raf/genetics, Melanoma/drug therapy, Melanoma/genetics, Melanoma/pathology, Protein Kinase Inhibitors/pharmacology, Protein Kinase Inhibitors/therapeutic use, Mitogen-Activated Protein Kinase Kinases, Ovarian Neoplasms/drug therapy, Ovarian Neoplasms/genetics, Mutation, BRAF, Ovarian cancer, adaptation, resistance
Pubmed
Web of science
Open Access
Yes
Create date
28/03/2023 12:30
Last modification date
20/09/2023 6:09