PARP inhibitors: Clinical utility and possibilities of overcoming resistance.
PARP inhibitors: Clinical utility and possibilities of overcoming resistance.
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DOI：
10.1016/j.ygyno.2017.10.003
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发表时间：
2017-12
影响因子：
4.7
通讯作者：
Behbakht K
中科院分区：
文献类型：
--
作者：
Bitler BG;Watson ZL;Wheeler LJ;Behbakht K
PARP 抑制剂代表了卵巢癌治疗的重大突破。几乎一半的卵巢癌都存在同源重组 (HR) DNA 修复途径缺陷，即 BRCA1/2 突变。鉴于复发性卵巢癌患者的治疗选择有限，人们付出了巨大的努力来开发新的疗法来利用 DNA 修复缺陷。 2005 年和 2006 年，首次观察到抑制 PARP 酶对 HR 缺陷的癌症非常有效。 PARP 抑制剂在临床上用于治疗 HR 修复途径缺陷的复发性卵巢癌。然而，PARP 抑制剂对没有 HR 缺陷的患者也显示出显着的临床益处。目前，FDA 批准了三种用于治疗复发性卵巢癌的 PARP 抑制剂，另外两种 PARP 抑制剂正在后期临床试验中进行评估。鉴于 PARP 抑制剂临床应用的不断扩大以及获得性耐药的可能性很高，因此非常需要临床策略来管理 PARP 抑制剂耐药性疾病。本综述将在以下方面研究 PARP 抑制剂：适应症和毒性、预测反应的新型生物标志物、靶向治疗耐药性以及管理耐药性疾病的潜在方法。
PARP inhibitors represent a major breakthrough in ovarian cancer care. Almost half of all ovarian cancers have deficiencies in the homologous recombination (HR) DNA repair pathway, namely BRCA1/2 mutations. Given the limited therapeutic options for recurrent ovarian cancer patients there has been a significant effort to develop novel therapies to exploit DNA repair deficiencies. In 2005 and 2006, inhibiting PARP enzymes was first observed to be highly effective against cancers with HR deficiencies. PARP inhibitors are being utilized in the clinic to manage recurrent ovarian cancers that display defects in the HR repair pathway. However, PARP inhibitors also show significant clinical benefit in patients without HR deficiencies. There are currently three FDA-approved PARP inhibitors for recurrent ovarian cancer and an additional two PARP inhibitors being evaluated in late stage clinical trials. Given the expanding clinical use of PARP inhibitors and the high likelihood of acquired resistance, there is a significant need for clinical strategies to manage PARP inhibitor resistant disease. This review will examine PARP inhibitors in the context of: indications and toxicities, novel biomarkers to predict response, targeted-therapy resistance, and potential approaches to manage resistant disease.
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DOI：
10.1186/s40661-017-0039-8
发表时间：
2017
期刊：
Gynecologic oncology research and practice
影响因子：
--
作者：
Frey MK;Pothuri B
通讯作者：
Pothuri B
影响因子：
--
作者：
Aguilar-Quesada R;Muñoz-Gámez JA;Martín-Oliva D;Peralta A;Valenzuela MT;Matínez-Romero R;Quiles-Pérez R;Menissier-de Murcia J;de Murcia G;Ruiz de Almodóvar M;Oliver FJ
通讯作者：
Oliver FJ
影响因子：
82.9
作者：
Du Y;Yamaguchi H;Wei Y;Hsu JL;Wang HL;Hsu YH;Lin WC;Yu WH;Leonard PG;Lee GR 4th;Chen MK;Nakai K;Hsu MC;Chen CT;Sun Y;Wu Y;Chang WC;Huang WC;Liu CL;Chang YC;Chen CH;Park M;Jones P;Hortobagyi GN;Hung MC
通讯作者：
Hung MC
影响因子：
64.8
作者：
Ray Chaudhuri A;Callen E;Ding X;Gogola E;Duarte AA;Lee JE;Wong N;Lafarga V;Calvo JA;Panzarino NJ;John S;Day A;Crespo AV;Shen B;Starnes LM;de Ruiter JR;Daniel JA;Konstantinopoulos PA;Cortez D;Cantor SB;Fernandez-Capetillo O;Ge K;Jonkers J;Rottenberg S;Sharan SK;Nussenzweig A
通讯作者：
Nussenzweig A
影响因子：
5.3
作者：
AVEMANN, K;KNIPPERS, R;SOGO, JM
通讯作者：
SOGO, JM