Veliparib (ABT-888), a PARP inhibitor potentiates the cytotoxic activity of 5-fluorouracil by inhibiting MMR pathway through deregulation of MSH6 in colorectal cancer stem cells.
Expert Opin Ther Targets
; 27(10): 999-1015, 2023.
Article
in En
| MEDLINE
| ID: mdl-37787493
5-FU is a well-known drug commonly used to treat colorectal cancer and it causes DNA damage inside the cancer cells. The limitation of 5-FU treatment is the development of chemoresistance due to the high DNA repair capacity of cancer stem cells present in the tumor microenvironment. In this study, a novel chemotherapeutic approach has been developed to target colorectal cancer stem cells by using a combination of 5-FU and a PARP1 inhibitor (ABT-888). Here, 5-FU caused DNA damage and ABT-888 enhanced the accumulation of the DNA lesions by inhibiting the MMR repair pathway in 5-FU-pre-treated MMR-proficient-CRC-CSCs. This resulted in S-phase arrest, induction of apoptosis, and finally CSCs death.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Colorectal Neoplasms
/
Antineoplastic Agents
Limits:
Humans
Language:
En
Journal:
Expert Opin Ther Targets
Journal subject:
TERAPEUTICA
Year:
2023
Document type:
Article
Affiliation country:
India