Mapping combinatorial drug effects to DNA damage response kinase inhibitors.
Nat Commun
; 14(1): 8310, 2023 Dec 14.
Article
em En
| MEDLINE
| ID: mdl-38097586
ABSTRACT
One fundamental principle that underlies various cancer treatments, such as traditional chemotherapy and radiotherapy, involves the induction of catastrophic DNA damage, leading to the apoptosis of cancer cells. In our study, we conduct a comprehensive dose-response combination screening focused on inhibitors that target key kinases involved in the DNA damage response (DDR) ATR, ATM, and DNA-PK. This screening involves 87 anti-cancer agents, including six DDR inhibitors, and encompasses 62 different cell lines spanning 12 types of tumors, resulting in a total of 17,912 combination treatment experiments. Within these combinations, we analyze the most effective and synergistic drug pairs across all tested cell lines, considering the variations among cancers originating from different tissues. Our analysis reveals inhibitors of five DDR-related pathways (DNA topoisomerase, PLK1 kinase, p53-inducible ribonucleotide reductase, PARP, and cell cycle checkpoint proteins) that exhibit strong combinatorial efficacy and synergy when used alongside ATM/ATR/DNA-PK inhibitors.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas de Ciclo Celular
/
Neoplasias
Limite:
Humans
Idioma:
En
Revista:
Nat Commun
Assunto da revista:
BIOLOGIA
/
CIENCIA
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Estados Unidos
País de publicação:
ENGLAND
/
ESCOCIA
/
GB
/
GREAT BRITAIN
/
INGLATERRA
/
REINO UNIDO
/
SCOTLAND
/
UK
/
UNITED KINGDOM