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Ref Type Journal Article
PMID (36967525)
Authors Anchisi S, Wolfer A, Bisig B, Missiglia E, Tiab A, Kamel EM, Michielin O, Coukos G, Homicsko K
Title Deep and lasting response and acquired resistance to BRAFV600E targeting in a low-grade ovarian cancer patient.
Journal Vol Issue Date Pages Journal Short Title
Cancer biology & therapy 24 1 2023 Dec 31 2193116 Cancer Biol Ther
URL
Abstract Text 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.

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
BRAF V600E ovarian serous cystadenocarcinoma predicted - sensitive Vemurafenib Case Reports/Case Series Actionable In a clinical case study, Zelboraf (vemurafenib) treatment resulted in a complete radiological response that lasted for 3 years in a patient with low-grade serous cystadenocarcinoma of the ovary harboring BRAF V600E (PMID: 36967525). 36967525