- 作者: Yu-Yi Chu, Clinton Yam, Hirohito Yamaguchi & Mien-Chie Hung
- 作者服務機構: 1.Department of Biotechnology, Asia University, Taichung, 413, Taiwan 2.Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA 3.Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA 4.Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA 5.Research Center for Cancer Biology, and Center for Molecular Medicine, Graduate Institute of Biomedical Sciences, China Medical University, 100, Sec 1, Jingmao Rd., Beitun, Taichung, 40402, Taiwan, ROC
- 中文摘要:
- 英文摘要:
Poly (ADP-ribose) polymerase (PARP) inhibitors (PARPi) exploit the concept of synthetic lethality and ofer great
promise in the treatment of tumors with defciencies in homologous recombination (HR) repair. PARPi exert antitumor
activity by blocking Poly(ADP-ribosyl)ation (PARylation) and trapping PARP1 on damaged DNA. To date, the U.S. Food
and Drug Administration (FDA) has approved four PARPi for the treatment of several cancer types including ovarian,
breast, pancreatic and prostate cancer. Although patients with HR-defcient tumors beneft from PARPi, majority of
tumors ultimately develop acquired resistance to PARPi. Furthermore, even though BRCA1/2 mutations are commonly
used as markers of PARPi sensitivity in current clinical practice, not all patients with BRCA1/2 mutations have PARPisensitive disease. Thus, there is an urgent need to elucidate the molecular mechanisms of PARPi resistance to support
the development of rational efective treatment strategies aimed at overcoming resistance to PARPi, as well as reliable
biomarkers to accurately identify patients who will most likely beneft from treatment with PARPi, either as mono‑
therapy or in combination with other agents, so called marker-guided efective therapy (Mget). In this review, we
summarize the molecular mechanisms driving the efcacy of and resistance to PARPi as well as emerging therapeutic
strategies to overcome PARPi resistance. We also highlight the identifcation of potential markers to predict PARPi
resistance and guide promising PARPi-based combination strategies - 中文關鍵字:
- 英文關鍵字: PARP inhibitor, Resistance to PARP inhibitor, Biomarkers, PARPi-based combination strategies, Markerguided efective therapy (Mget)