Oncology, Centre Hospitalier du Valais Romand, Sion, Switzerland.
Swiss Agency for Therapeutic Products, SwissMedic, Bern, Switzerland.
Cancer Biol Ther. 2023 Dec 31;24(1):2193116. doi: 10.1080/15384047.2023.2193116.
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.
BRAF 抑制剂彻底改变了 BRAFV600E 突变型黑色素瘤的治疗方法。此外，BRAF/MEK 联合治疗在晚期和辅助黑色素瘤患者的临床结局中显示出了进一步的改善。在低级别卵巢肿瘤中，也提出了使用 BRAF 抑制剂。在这里，我们介绍了一位患者，她对单独使用 BRAF 治疗有极好且持久的反应。在最初进展后，在单独使用 BRAF 治疗两年多后，我们无法确定任何分子机制来解释耐药性。在切换到双 BRAF/MEK 治疗后，患者有了反应。然而，尽管最初的反应很明显，患者再次进展，这次出现了 KRAS G12C 突变，这一突变无法通过 BRAF/MEK 治疗克服。我们提供的证据表明，BRAF 抑制剂单独使用对 BRAF 突变型低级别卵巢肿瘤非常有效，耐药机制与其他 BRAF 突变型肿瘤（包括黑色素瘤）相似。
Zotero 插件