PARP Inhibitors in Pancreatic Cancer: From Phase I to Plenary Session.

Pancreas (Fairfax, Va.) Pub Date : 2019-01-01 Epub Date: 2019-12-20 DOI:10.17140/POJ-3-e011
Rajvi Patel, Daniel Fein, Carolina B Ramirez, Kevin Do, Muhammad W Saif
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引用次数: 13

Abstract

Survival rates for pancreatic cancer remain dismal. Current standard of care treatment regimens provide transient clinical benefit but eventually chemoresistance develops. Tumors deficient in deoxyribonucleic acid (DNA) damage repair mechanisms such as BRCA mutants show better responses to platinum based agents, however, such tumors can utilize the poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) pathway as a salvage mechanism. Therefore, inhibition of PARP pathway could lead to tumor destruction and synthetic lethality in presence of BRCA mutation. Various PARP inhibitors have been approved for treatment of patients with germline or somatic BRCA mutant breast and ovarian cancer. This provides basis of using PARP inhibitors in patients with pancreatic cancer that harbor BRCA mutation. A recent phase III Pancreas Cancer Olaparib Ongoing (POLO) study showed impressive results with near doubling of progression free survival compared to placebo (7.4 vs 3.8 months). These results highlight the importance of germline testing for all patients with pancreatic cancer and inclusion of additional deficiencies in homologous recombination repair (ATM and PALB2) including BRCA variants of uncertain significance should be further explored.

Abstract Image

PARP抑制剂在胰腺癌中的应用:从I期到全体会议
胰腺癌的存活率仍然很低。目前的标准护理治疗方案提供短暂的临床益处,但最终会产生化疗耐药。缺乏脱氧核糖核酸(DNA)损伤修复机制的肿瘤,如BRCA突变体,对铂类药物表现出更好的反应,然而,这类肿瘤可以利用聚二磷酸腺苷[ADP]-核糖)聚合酶(PARP)途径作为挽救机制。因此,在BRCA突变存在的情况下,抑制PARP通路可导致肿瘤破坏和合成致死。各种PARP抑制剂已被批准用于治疗生殖系或体细胞BRCA突变乳腺癌和卵巢癌患者。这为在BRCA突变的胰腺癌患者中使用PARP抑制剂提供了依据。最近的一项III期胰腺癌奥拉帕尼(POLO)研究显示了令人印象深刻的结果,与安慰剂相比,无进展生存期几乎翻了一番(7.4个月对3.8个月)。这些结果强调了种系检测对所有胰腺癌患者的重要性,并强调了同源重组修复(ATM和PALB2)的其他缺陷(包括不确定意义的BRCA变异)应进一步探讨。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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