Moschetta Michele, Mak Gabriel, Hauser Joana, Davies Catriona, Uccello Mario, Arkenau Hendrik-Tobias
Drug Development Unit, Sarah Cannon Research Institute, 93 Harley Street, London, W1G 6AD UK ; University College London, London, UK.
Drug Development Unit, Sarah Cannon Research Institute, 93 Harley Street, London, W1G 6AD UK.
Exp Hematol Oncol. 2017 Jan 10;6:1. doi: 10.1186/s40164-016-0061-2. eCollection 2017.
Targeting 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.
We 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.
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.
靶向BRAF V600E突变已被证明在多种癌症治疗中有效。在子宫内膜腺癌中，BRAF V600E突变鲜有报道。对于罕见的BRAF突变型子宫内膜癌患者，靶向BRAF癌基因是否可能成为一种可行的治疗策略仍有待前瞻性研究确定。
我们在此报告一例经过大量前期治疗的复发性微卫星高度不稳定（MSI-H）BRAF V600E突变型子宫内膜腺癌患者，该患者用V600E靶向药物达拉非尼成功治疗。在对该药物产生耐药后，将MEK靶向药物曲美替尼添加到达拉非尼中，再次实现了治疗反应。
该病例表明，达拉非尼单药治疗以及与曲美替尼联合使用时，对经过大量前期治疗的BRAF V600E突变型子宫内膜腺癌可能具有显著的治疗活性，并突出了该疾病个性化治疗的潜在益处。
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