Frontiers in Oncology (Aug 2024)
Combined strategies with PARP inhibitors for the treatment of BRCA wide type cancer
- Yijun Xie,
- Yijun Xie,
- Yijun Xie,
- Yijun Xie,
- Yijun Xie,
- Yijun Xie,
- Yijun Xie,
- Di Xiao,
- Di Xiao,
- Di Xiao,
- Di Xiao,
- Di Xiao,
- Di Xiao,
- Di Xiao,
- Duo Li,
- Duo Li,
- Duo Li,
- Duo Li,
- Duo Li,
- Duo Li,
- Duo Li,
- Mei Peng,
- Mei Peng,
- Mei Peng,
- Mei Peng,
- Mei Peng,
- Mei Peng,
- Mei Peng,
- Wei Peng,
- Wei Peng,
- Wei Peng,
- Wei Peng,
- Wei Peng,
- Wei Peng,
- Wei Peng,
- Huaxin Duan,
- Huaxin Duan,
- Huaxin Duan,
- Huaxin Duan,
- Huaxin Duan,
- Huaxin Duan,
- Huaxin Duan,
- Xiaoping Yang,
- Xiaoping Yang,
- Xiaoping Yang,
- Xiaoping Yang,
- Xiaoping Yang,
- Xiaoping Yang,
- Xiaoping Yang
Affiliations
- Yijun Xie
- Department of Oncology, Hunan Provincial People’s Hospital, The First Affiliated Hospital of Hunan Normal University, Hunan Normal University, Changsha, Hunan, China
- Yijun Xie
- Key Laboratory of Study and Discovery of Small Targeted Molecules of Hunan Province, Hunan Normal University, Changsha, Hunan, China
- Yijun Xie
- Engineering Research Center of Reproduction and Translational Medicine of Hunan Province, Hunan Normal University, Changsha, Hunan, China
- Yijun Xie
- Key Laboratory of Chemical Biology & Traditional Chinese Medicine Research of Ministry of Education, Hunan Normal University, Changsha, Hunan, China
- Yijun Xie
- Key Laboratory of Protein Chemistry and Developmental Biology of Fish of Ministry of Education, Hunan Normal University, Changsha, Hunan, China
- Yijun Xie
- Department of Pharmacy, Hunan Normal University, Changsha, Hunan, China
- Yijun Xie
- School of Medicine, Hunan Normal University, Changsha, Hunan, China
- Di Xiao
- Department of Oncology, Hunan Provincial People’s Hospital, The First Affiliated Hospital of Hunan Normal University, Hunan Normal University, Changsha, Hunan, China
- Di Xiao
- Key Laboratory of Study and Discovery of Small Targeted Molecules of Hunan Province, Hunan Normal University, Changsha, Hunan, China
- Di Xiao
- Engineering Research Center of Reproduction and Translational Medicine of Hunan Province, Hunan Normal University, Changsha, Hunan, China
- Di Xiao
- Key Laboratory of Chemical Biology & Traditional Chinese Medicine Research of Ministry of Education, Hunan Normal University, Changsha, Hunan, China
- Di Xiao
- Key Laboratory of Protein Chemistry and Developmental Biology of Fish of Ministry of Education, Hunan Normal University, Changsha, Hunan, China
- Di Xiao
- Department of Pharmacy, Hunan Normal University, Changsha, Hunan, China
- Di Xiao
- School of Medicine, Hunan Normal University, Changsha, Hunan, China
- Duo Li
- Department of Oncology, Hunan Provincial People’s Hospital, The First Affiliated Hospital of Hunan Normal University, Hunan Normal University, Changsha, Hunan, China
- Duo Li
- Key Laboratory of Study and Discovery of Small Targeted Molecules of Hunan Province, Hunan Normal University, Changsha, Hunan, China
- Duo Li
- Engineering Research Center of Reproduction and Translational Medicine of Hunan Province, Hunan Normal University, Changsha, Hunan, China
- Duo Li
- Key Laboratory of Chemical Biology & Traditional Chinese Medicine Research of Ministry of Education, Hunan Normal University, Changsha, Hunan, China
- Duo Li
- Key Laboratory of Protein Chemistry and Developmental Biology of Fish of Ministry of Education, Hunan Normal University, Changsha, Hunan, China
- Duo Li
- Department of Pharmacy, Hunan Normal University, Changsha, Hunan, China
- Duo Li
- School of Medicine, Hunan Normal University, Changsha, Hunan, China
- Mei Peng
- Department of Oncology, Hunan Provincial People’s Hospital, The First Affiliated Hospital of Hunan Normal University, Hunan Normal University, Changsha, Hunan, China
- Mei Peng
- Key Laboratory of Study and Discovery of Small Targeted Molecules of Hunan Province, Hunan Normal University, Changsha, Hunan, China
- Mei Peng
- Engineering Research Center of Reproduction and Translational Medicine of Hunan Province, Hunan Normal University, Changsha, Hunan, China
- Mei Peng
- Key Laboratory of Chemical Biology & Traditional Chinese Medicine Research of Ministry of Education, Hunan Normal University, Changsha, Hunan, China
- Mei Peng
- Key Laboratory of Protein Chemistry and Developmental Biology of Fish of Ministry of Education, Hunan Normal University, Changsha, Hunan, China
- Mei Peng
- Department of Pharmacy, Hunan Normal University, Changsha, Hunan, China
- Mei Peng
- School of Medicine, Hunan Normal University, Changsha, Hunan, China
- Wei Peng
- Department of Oncology, Hunan Provincial People’s Hospital, The First Affiliated Hospital of Hunan Normal University, Hunan Normal University, Changsha, Hunan, China
- Wei Peng
- Key Laboratory of Study and Discovery of Small Targeted Molecules of Hunan Province, Hunan Normal University, Changsha, Hunan, China
- Wei Peng
- Engineering Research Center of Reproduction and Translational Medicine of Hunan Province, Hunan Normal University, Changsha, Hunan, China
- Wei Peng
- Key Laboratory of Chemical Biology & Traditional Chinese Medicine Research of Ministry of Education, Hunan Normal University, Changsha, Hunan, China
- Wei Peng
- Key Laboratory of Protein Chemistry and Developmental Biology of Fish of Ministry of Education, Hunan Normal University, Changsha, Hunan, China
- Wei Peng
- Department of Pharmacy, Hunan Normal University, Changsha, Hunan, China
- Wei Peng
- School of Medicine, Hunan Normal University, Changsha, Hunan, China
- Huaxin Duan
- Department of Oncology, Hunan Provincial People’s Hospital, The First Affiliated Hospital of Hunan Normal University, Hunan Normal University, Changsha, Hunan, China
- Huaxin Duan
- Key Laboratory of Study and Discovery of Small Targeted Molecules of Hunan Province, Hunan Normal University, Changsha, Hunan, China
- Huaxin Duan
- Engineering Research Center of Reproduction and Translational Medicine of Hunan Province, Hunan Normal University, Changsha, Hunan, China
- Huaxin Duan
- Key Laboratory of Chemical Biology & Traditional Chinese Medicine Research of Ministry of Education, Hunan Normal University, Changsha, Hunan, China
- Huaxin Duan
- Key Laboratory of Protein Chemistry and Developmental Biology of Fish of Ministry of Education, Hunan Normal University, Changsha, Hunan, China
- Huaxin Duan
- Department of Pharmacy, Hunan Normal University, Changsha, Hunan, China
- Huaxin Duan
- School of Medicine, Hunan Normal University, Changsha, Hunan, China
- Xiaoping Yang
- Department of Oncology, Hunan Provincial People’s Hospital, The First Affiliated Hospital of Hunan Normal University, Hunan Normal University, Changsha, Hunan, China
- Xiaoping Yang
- Key Laboratory of Study and Discovery of Small Targeted Molecules of Hunan Province, Hunan Normal University, Changsha, Hunan, China
- Xiaoping Yang
- Engineering Research Center of Reproduction and Translational Medicine of Hunan Province, Hunan Normal University, Changsha, Hunan, China
- Xiaoping Yang
- Key Laboratory of Chemical Biology & Traditional Chinese Medicine Research of Ministry of Education, Hunan Normal University, Changsha, Hunan, China
- Xiaoping Yang
- Key Laboratory of Protein Chemistry and Developmental Biology of Fish of Ministry of Education, Hunan Normal University, Changsha, Hunan, China
- Xiaoping Yang
- Department of Pharmacy, Hunan Normal University, Changsha, Hunan, China
- Xiaoping Yang
- School of Medicine, Hunan Normal University, Changsha, Hunan, China
- DOI
- https://doi.org/10.3389/fonc.2024.1441222
- Journal volume & issue
-
Vol. 14
Abstract
Genomic instability stands out as a pivotal hallmark of cancer, and PARP inhibitors (PARPi) emerging as a groundbreaking class of targeted therapy drugs meticulously crafted to inhibit the repair of DNA single-strand breaks(SSB) in tumor cells. Currently, PARPi have been approved for the treatment of ovarian cancer, pancreatic cancer, breast cancer, and prostate cancer characterized by homologous recombination(HR) repair deficiencies due to mutations in BRCA1/2 or other DNA repair associated genes and acquiring the designation of breakthrough therapy. Nonetheless, PARPi exhibit limited efficacy in the majority of HR-proficient BRCA1/2 wild-type cancers. At present, the synergistic approach of combining PARPi with agents that induce HR defects, or with chemotherapy and radiotherapy to induce substantial DNA damage, significantly enhances the efficacy of PARPi in BRCA wild-type or HR-proficient patients, supporting extension the use of PARPi in HR proficient patients. Therefore, we have summarized the effects and mechanisms of the combined use of drugs with PARPi, including the combination of PARPi with HR defect-inducing drugs such as ATRi, CHKi, HR indirectly inducing drugs like VEGFRi, CDKi, immune checkpoint inhibitors and drugs instigating DNA damage such as chemotherapy or radiotherapy. In addition, this review discusses several ongoing clinical trials aimed at analyzing the clinical application potential of these combined treatment strategies.
Keywords