臨床婦人科産科71巻11号

2017年11月発行

今月の臨床 遺伝子診療の最前線─着床前，胎児から婦人科がんまで

婦人科腫瘍

卵巣がんのゲノム解析と分子標的治療

著者： 織田克利¹

所属機関： ¹東京大学大学院医学系研究科産婦人科学講座

ページ範囲：P.1038 - P.1043

文献概要

●分子標的治療薬では感受性を予測するバイオマーカーが重要である．

●DNA修復にかかわる特定の遺伝子（BRCA1/2やミスマッチ修復遺伝子など）の生殖細胞系変異は，分子標的治療薬のバイオマーカーとなりうる．

●PARP阻害薬と免疫チェックポイント阻害薬は，今後の臨床応用が期待される分子標的治療薬である．

参考文献

1）Cancer Genome Atlas Research Network : Integrated genomic analyses of ovarian carcinoma. Nature 474 : 609─615, 2011

2）Patch AM, et al : Whole-genome characterization of chemoresistant ovarian cancer. Nature 521 : 489─494, 2015

3）Ledermann J, et al : Olaparib maintenance therapy in platinum-sensitive relapsed ovarian cancer. N Engl J Med 366 : 1382─1392, 2012

4）Swisher EM, et al : Rucaparib in relapsed, platinum-sensitive high-grade ovarian carcinoma（ARIEL2 Part 1） : an international, multicentre, open-label, phase 2 trial. Lancet Oncol 18 : 75─87, 2017

5）Kim G, et al : FDA approval summary : olaparib monotherapy in patients with deleterious germline BRCA-mutated advanced ovarian cancer treated with three or more lines of chemotherapy. Clin Cancer Res 21 : 4257─4261, 2015

6）Pujade-Lauraine E, et al : Olaparib tablets as maintenance therapy in patients with platinum-sensitive, relapsed ovarian cancer and a BRCA1/2 mutation（SOLO2/ENGOT-Ov21）: a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Oncol 2017［Epub ahead of print］

7）Mirza MR, et al : Niraparib maintenance therapy in platinum-sensitive, recurrent ovarian cancer. N Engl J Med 375 : 2154─2164, 2016

8）Hamanishi J, et al : Safety and antitumor activity of anti-PD-1 antibody, nivolumab, in patients with platinum-resistant ovarian cancer. J Clin Oncol 33 : 4015─4022, 2015

9）Alexandrov LB, et al : Signatures of mutational processes in human cancer. Nature 500 : 415─421, 2013

10）Dudley JC, et al : Microsatellite instability as a biomarker for PD-1 blockade. Clin Cancer Res 22 : 813─820, 2016

11）Matsushita H, et al : The frequency of neoantigens per somatic mutation rather than overall mutational load or number of predicted neoantigens per se is a prognostic factor in ovarian clear cell carcinoma. Oncoimmunology, 2017

12）Kommoss S, et al : Bevacizumab may differentially improve ovarian cancer outcome in patients with proliferative and mesenchymal molecular subtypes. Clin Cancer Res 23 : 3794─3801, 2017