Lightfoot Michelle, Montemorano Lauren, Bixel Kristin
Ohio State Wexner Medical Center, M210 Starling Loving Hall, 320 West 10th Avenue, Columbus, OH-43210, USA.
Curr Oncol Rep. 2020 Feb 17;22(3):29. doi: 10.1007/s11912-020-0873-4.
Conventional and novel applications of Poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitors (PARPi) are reviewed in the context of recently published clinical trials and preclinical data supporting rapidly expanding uses of this class of chemotherapy.
PARPi block a pathway of DNA repair and target defects in homologous recombination repair (HRR), a pathway responsible for high-fidelity repair of double-strand breaks in DNA. BRCA1/2 proteins are essential to this pathway. Approximately 15-30% of women with ovarian cancer will have a germline or somatic BRCA mutation, and PARPi have shown promise in this population in a variety of settings. With growing understanding of the HRR pathway and its role in gynecologic malignancies, the potential applications of PARPi continue to expand. While the role of PARPi in gynecologic malignancies is most established in ovarian cancer, there are also promising applications in uterine and cervical cancer. We review current indications for PARPi use and promising applications of these medications in gynecologic malignancies.
在近期发表的临床试验和临床前数据的背景下,综述聚(腺苷二磷酸[ADP] - 核糖)聚合酶(PARP)抑制剂(PARPi)的传统和新应用,这些数据支持这类化疗药物的使用正在迅速扩大。
PARPi阻断DNA修复途径,并靶向同源重组修复(HRR)中的缺陷,HRR是负责DNA双链断裂高保真修复的途径。BRCA1/2蛋白对该途径至关重要。约15% - 30%的卵巢癌女性会有胚系或体细胞BRCA突变,PARPi在该人群的多种情况下已显示出前景。随着对HRR途径及其在妇科恶性肿瘤中作用的认识不断加深,PARPi的潜在应用持续扩大。虽然PARPi在妇科恶性肿瘤中的作用在卵巢癌中最为明确,但在子宫癌和宫颈癌中也有有前景的应用。我们综述PARPi目前的使用指征以及这些药物在妇科恶性肿瘤中的有前景的应用。