Shaping DNA damage responses: Therapeutic potential of targeting telomeric proteins and DNA repair factors in cancer.
Curr Opin Pharmacol
; 76: 102460, 2024 Jun.
Article
em En
| MEDLINE
| ID: mdl-38776747
ABSTRACT
Shelterin proteins regulate genomic stability by preventing inappropriate DNA damage responses (DDRs) at telomeres. Unprotected telomeres lead to persistent DDR causing cell cycle inhibition, growth arrest, and apoptosis. Cancer cells rely on DDR to protect themselves from DNA lesions and exogenous DNA-damaging agents such as chemotherapy and radiotherapy. Therefore, targeting DDR machinery is a promising strategy to increase the sensitivity of cancer cells to existing cancer therapies. However, the success of these DDR inhibitors depends on other mutations, and over time, patients develop resistance to these therapies. This suggests the need for alternative approaches. One promising strategy is co-inhibiting shelterin proteins with DDR molecules, which would offset cellular fitness in DNA repair in a mutation-independent manner. This review highlights the associations and dependencies of the shelterin complex with the DDR proteins and discusses potential co-inhibition strategies that might improve the therapeutic potential of current inhibitors.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Dano ao DNA
/
Reparo do DNA
/
Neoplasias
/
Antineoplásicos
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Curr Opin Pharmacol
Ano de publicação:
2024
Tipo de documento:
Article