DNA repair pathways and cisplatin resistance: an intimate relationship

Author(s)

Reily Rocha, Clarissa Ribeiro ^[1] ; Silva, Matheus Molina ^[1] ; Quinet, Annabel ^[1] ; Cabral-Neto, Januario Bispo ^[2] ; Martins Menck, Carlos Frederico ^[1]

Affiliation

^[1] Univ Sao Paulo, Inst Ciencias Biomed, Dept Microbiol, Sao Paulo, SP - Brazil

^[2] Univ Fed Rio de Janeiro UFRJ, Inst Biofis Carlos Chagas Filho, Rio De Janeiro, RJ - Brazil

• Document type: Review article
• Source: Clinics; v. 73, n. 1 2018.
• Web of Science Citations: 26

Abstract

The main goal of chemotherapeutic drugs is to induce massive cell death in tumors. Cisplatin is an antitumor drug widely used to treat several types of cancer. Despite its remarkable efficiency, most tumors show intrinsic or acquired drug resistance. The primary biological target of cisplatin is genomic DNA, and it causes a plethora of DNA lesions that block transcription and replication. These cisplatin-induced DNA lesions strongly induce cell death if they are not properly repaired or processed. To counteract cisplatin-induced DNA damage, cells use an intricate network of mechanisms, including DNA damage repair and translesion synthesis. In this review, we describe how cisplatin-induced DNA lesions are repaired or tolerated by cells and focus on the pivotal role of DNA repair and tolerance mechanisms in tumor resistance to cisplatin. In fact, several recent clinical findings have correlated the tumor cell status of DNA repair/translesion synthesis with patient response to cisplatin treatment. Furthermore, these mechanisms provide interesting targets for pharmacological modulation that can increase the efficiency of cisplatin chemotherapy. (AU)

• FAPESP's process: 14/15982-6 - Consequences of repair deficiencies in damaged genome
• Grantee: Carlos Frederico Martins Menck
• Support Opportunities: Research Projects - Thematic Grants