Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA, 94305, USA.
Cancer Biology Laboratory, School of Life Sciences, Jawaharlal Nehru University, New Delhi, 110067, India.
Oncol Res. 2023 Jun 27;31(4):405-421. doi: 10.32604/or.2023.028310. eCollection 2023.
Ionizing radiation is frequently used to treat solid tumors, as it causes DNA damage and kill cancer cells. However, damaged DNA is repaired involving poly-(ADP-ribose) polymerase-1 (PARP-1) causing resistance to radiation therapy. Thus, PARP-1 represents an important target in multiple cancer types, including prostate cancer. PARP is a nuclear enzyme essential for single-strand DNA breaks repair. Inhibiting PARP-1 is lethal in a wide range of cancer cells that lack the homologous recombination repair (HR) pathway. This article provides a concise and simplified overview of the development of PARP inhibitors in the laboratory and their clinical applications. We focused on the use of PARP inhibitors in various cancers, including prostate cancer. We also discussed some of the underlying principles and challenges that may affect the clinical efficacy of PARP inhibitors.
电离辐射常用于治疗实体肿瘤,因为它会导致 DNA 损伤并杀死癌细胞。然而,受损的 DNA 通过多聚(ADP-核糖)聚合酶-1(PARP-1)修复,从而导致对放射治疗的耐药性。因此,PARP-1 是包括前列腺癌在内的多种癌症类型中的一个重要靶点。PARP 是核酶,对单链 DNA 断裂修复至关重要。抑制 PARP-1 在缺乏同源重组修复(HR)途径的广泛癌症细胞中是致命的。本文简要概述了 PARP 抑制剂在实验室中的发展及其临床应用。我们重点介绍了 PARP 抑制剂在各种癌症中的应用,包括前列腺癌。我们还讨论了一些可能影响 PARP 抑制剂临床疗效的基本原理和挑战。