Successful use of next generation genomic sequencing (NGS)-directed therapy of clear cell carcinoma of the ovary (CCCO) with trametinib and metformin in a patient with chemotherapy-refractory disease.

Gynecologic oncology research and practice Pub Date : 2015-08-28 eCollection Date: 2015-01-01 DOI:10.1186/s40661-015-0013-2
Michael P Castro, Bradford P Whitcomb, Deborah A Zajchowski, Robert L Coleman
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引用次数: 11

Abstract

Purpose: Compared to other subtypes of epithelial ovarian cancer, clear cell carcinoma of the ovary bears an ominous reputation for chemotherapy resistance, increased relapse rate, and diminished survival. Among patients with distinct histopathologic subtypes, molecular analyses have identified a variety of known drivers of the malignant behavior, and depict a striking heterogeneity.

Methods: A patient with rapidly metastatic CCCO that was refractory to taxane, platinum, pemetrexed, and bevacizumab-based strategies underwent molecular profiling which disclosed dual MAPK and PI3K/AKT/mTOR pathway mutations.

Results: Combined targeted therapy with trametinib and metformin resulted in a dramatic disease regression without toxicity.

Conclusion: The case highlights the utility of precision medicine combining individual molecular diagnosis with rational therapeutic intervention with targeted agents.

Abstract Image

新一代基因组测序(NGS)指导下使用曲美替尼和二甲双胍治疗化疗难治性疾病患者卵巢透明细胞癌(CCCO)的成功应用
目的:与其他上皮性卵巢癌亚型相比,卵巢透明细胞癌具有化疗耐药、复发率增加和生存率降低的不良名声。在具有不同组织病理学亚型的患者中,分子分析已经确定了各种已知的恶性行为驱动因素,并描绘了惊人的异质性。方法:对紫杉烷、铂、培美曲塞和贝伐单抗为基础的策略难治性快速转移性CCCO患者进行了分子分析,发现双MAPK和PI3K/AKT/mTOR通路突变。结果:曲美替尼和二甲双胍联合靶向治疗使疾病显著消退,无毒性。结论:该病例凸显了精准医学结合个体分子诊断与靶向药物的合理治疗干预的实用性。
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