DNA repair pathways and cisplatin resistance

an intimate relationship

Authors

  • Clarissa Ribeiro Reily Rocha Universidade de Sao Paulo. Instituto de Ciencias Biomedicas. Departamento de Microbiologia
  • Matheus Molina Silva Universidade de Sao Paulo. Instituto de Ciencias Biomedicas. Departamento de Microbiologia
  • Annabel Quinet Universidade de Sao Paulo. Instituto de Ciencias Biomedicas. Departamento de Microbiologia
  • Januario Bispo Cabral-Neto Universidade Federal do Rio de Janeiro. Instituto de Biofisica Carlos Chagas Filho
  • Carlos Frederico Martins Menck Universidade de Sao Paulo. Instituto de Ciencias Biomedicas. Departamento de Microbiologia

DOI:

https://doi.org/10.6061/clinics/2018/e478s

Keywords:

Cisplatin, Resistance, DNA Repair, DNA Damage Tolerance

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.

Downloads

Download data is not yet available.

Downloads

Published

2019-02-15

Issue

Section

Review Articles

How to Cite

Rocha, C. R. R., Silva, M. M., Quinet, A., Cabral-Neto, J. B., & Menck, C. F. M. (2019). DNA repair pathways and cisplatin resistance: an intimate relationship. Clinics, 73(Suppl. 1), e478s. https://doi.org/10.6061/clinics/2018/e478s