Cisplatin in the era of PARP inhibitors and immunotherapy

Mingrui Duan; Shuguang Leng; Peng Mao

doi:10.1016/j.pharmthera.2024.108642

Cisplatin in the era of PARP inhibitors and immunotherapy

Pharmacol Ther. 2024 Apr 15:258:108642. doi: 10.1016/j.pharmthera.2024.108642. Online ahead of print.

Authors

Mingrui Duan¹, Shuguang Leng², Peng Mao³

Affiliations

¹ Department of Internal Medicine, University of New Mexico, Albuquerque, NM 87131, USA; University of New Mexico Comprehensive Cancer Center, Albuquerque, NM 87131, USA.
² Department of Internal Medicine, University of New Mexico, Albuquerque, NM 87131, USA; University of New Mexico Comprehensive Cancer Center, Albuquerque, NM 87131, USA. Electronic address: SLeng@salud.unm.edu.
³ Department of Internal Medicine, University of New Mexico, Albuquerque, NM 87131, USA; University of New Mexico Comprehensive Cancer Center, Albuquerque, NM 87131, USA. Electronic address: PMao@salud.unm.edu.

PMID: 38614254
DOI: 10.1016/j.pharmthera.2024.108642

Abstract

Platinum compounds such as cisplatin, carboplatin and oxaliplatin are widely used in chemotherapy. Cisplatin induces cytotoxic DNA damage that blocks DNA replication and gene transcription, leading to arrest of cell proliferation. Although platinum therapy alone is effective against many tumors, cancer cells can adapt to the treatment and gain resistance. The mechanisms for cisplatin resistance are complex, including low DNA damage formation, high DNA repair capacity, changes in apoptosis signaling pathways, rewired cell metabolisms, and others. Drug resistance compromises the clinical efficacy and calls for new strategies by combining cisplatin with other therapies. Exciting progress in cancer treatment, particularly development of poly (ADP-ribose) polymerase (PARP) inhibitors and immune checkpoint inhibitors, opened a new chapter to combine cisplatin with these new cancer therapies. In this Review, we discuss how platinum synergizes with PARP inhibitors and immunotherapy to bring new hope to cancer patients.

Keywords: Chemo-immunotherapy; DNA damage; DNA repair; Poly (ADP-ribose) polymerase.

Publication types

Review