Abstract
BackgroundTargeting BRAF V600E mutation has been proven effective in the treatment of several types of cancer. In endometrial adenocarcinoma, the BRAF V600E mutation has been rarely reported. Whether targeting BRAF oncogene may represent a plausible therapeutic strategy for the rare patients with BRAF-mutated endometrial cancer remains to be ascertained in prospective studies.Case presentationWe report herein the case of a heavily pre-treated patient with recurrent microsatellite instability high (MSI-H) BRAF V600E mutated endometrial adenocarcinoma, which was successfully treated with the V600E targeting agent dabrafenib. After developing resistance to this agent, the MEK targeting agent trametinib was added to dabrafenib achieving again a therapeutic response.ConclusionsThis case shows that dabrafenib both as monotherapy and when combined with trametinib may exert significant therapeutic activity in heavily pretreated BRAF V600E mutated endometrial adenocarcinoma, and highlight potential benefits of personalized treatment in this disease.
Highlights
Targeting B-rapid accelerated fibrosarcoma (BRAF) V600E mutation has been proven effective in the treatment of several types of can‐ cer
This case shows that dabrafenib both as monotherapy and when combined with trametinib may exert significant therapeutic activity in heavily pretreated BRAF V600E mutated endometrial adenocarcinoma, and highlight potential benefits of personalized treatment in this disease
Agents targeting the BRAF V600E mutation can lead to impressive response rate in BRAF V600E mutated melanoma [5] and hairy cell leukemia [6], alone or when combined with a mitogen-activated protein/ extracellular signal-regulated kinase kinase (MEK) targeting agent [7]; intermediate activity has been observed in BRAF mutated non-small cell lung cancer [8] and thyroid cancer [9], while minimal activity has been achieved in BRAF V600E mutated colorectal cancers [10]
Summary
This case illustrates the importance of molecular characterization of sporadic cancers and the potential impact that personalized therapy can have on the prognosis of cancer bearing actionable mutations. This case shows that MAPK pathway plays a central role in the pathogenesis of a subset of endometrial cancers and that BRAF and MEK inhibitors may exert significant antitumor activity in BRAF V600E mutated endometrial cancers, calling for prospective confirmatory clinical studies to be carried out in this setting. All authors read and approved the final manuscript. Author details 1 Drug Development Unit, Sarah Cannon Research Institute, 93 Harley Street, London W1G 6AD, UK. Author details 1 Drug Development Unit, Sarah Cannon Research Institute, 93 Harley Street, London W1G 6AD, UK. 2 University College London, London, UK
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