PARP inhibitors as single agents and in combination therapy: the most promising treatment strategies in clinical trials for BRCA-mutant ovarian and triple-negative breast cancers.
PARP inhibitors as single agents and in combination therapy: the most promising treatment strategies in clinical trials for BRCA-mutant ovarian and triple-negative breast cancers.
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DOI：
10.1080/13543784.2022.2067527
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发表时间：
2022-06
影响因子：
6.1
通讯作者：
Keyomarsi, Khandan
中科院分区：
文献类型：
--
作者：
Luo, Linjie;Keyomarsi, Khandan
关键词：
Clinical trialcombination therapyDNA damage repair (DDR)drug resistancegermline BRCA-mutationhigh-grade serous ovarian cancer (HGSOC)homologous recombination deficiency (HRD)niraparibolaparibpoly (ADP-ribose) polymerase (PARP) inhibitorpreclinical studysomatic BRCA-mutationtriple-negative breast cancer (TNBC)rucaparibtalazoparibveliparibpamiparibfluzoparibimmunotherapy
聚（ADP-核糖）聚合酶抑制剂（PARP）是一类令人兴奋的药物，已显示出疗效，特别是对BRCA突变型三阴性乳腺癌（TNBC）和高级别浆液性卵巢癌（HGSOC）。然而，大多数接受PARPi作为标准治疗的患者不可避免地产生耐药性，这强调了需要确定可以规避这种耐药性的其他靶标。联合治疗策略已在临床前和临床研究中开发，以解决疗效和耐药性的挑战。本综述检查了PARPi单药和联合治疗的已完成或正在进行的临床试验。PARPi单药治疗HER 2阴性乳腺癌（HR+和TNBC亚型）和卵巢癌是一个焦点。作者提出了可能克服PARPi阻力的潜在策略，并讨论了关键问题和未来方向。虽然PARPis的出现显着改善了DNA损伤和修复途径缺陷的肿瘤的治疗，但仔细选择患者对于增强这些治疗至关重要。鉴定分子生物标志物以预测疾病反应和进展是一项奋进。
Poly (ADP-ribose) polymerase inhibitors (PARPis) are an exciting class of agents that have shown efficacy, particularly for BRCA-mutant triple-negative breast cancer (TNBC) and high-grade serous ovarian cancer (HGSOC). However, most patients who receive PARPi as their standard of care therapy inevitably develop resistance and this underscores the need to identify additional targets that can circumvent such resistance. Combination treatment strategies have been developed in preclinical and clinical studies to address the challenges of efficacy and resistance. This review examines completed or ongoing clinical trials of PARPi mono- and combination therapies. PARPi monotherapy in HER2 negative breast (HR+ and TNBC subtypes) and ovarian cancer is a focal point. The authors propose potential strategies that might overcome resistance to PARPi and discuss key questions and future directions. While the advent of PARPis has significantly improved the treatment of tumors with defects in DNA damage and repair pathways, careful patient selection will be essential to enhance these treatments. The identification of molecular biomarkers to predict disease response and progression is an endeavor.
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影响因子：
19
作者：
Ceccaldi R;Rondinelli B;D'Andrea AD
通讯作者：
D'Andrea AD
影响因子：
45.3
作者：
Atchley, Deann P.;Albarracin, Constance T.;Arun, Banu K.
通讯作者：
Arun, Banu K.
影响因子：
8
作者：
Chow, J. P. H.;Poon, R. Y. C.
通讯作者：
Poon, R. Y. C.
DOI：
10.1038/nrm.2017.53
发表时间：
2017-10
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
Ray Chaudhuri A;Nussenzweig A
通讯作者：
Nussenzweig A
影响因子：
5.2
作者：
Chen X;Yang D;Carey JPW;Karakas C;Albarracin C;Sahin AA;Arun BK;Guray Durak M;Li M;Kohansal M;Bui TN;Ha MJ;Hunt KK;Keyomarsi K
通讯作者：
Keyomarsi K