Exploiting Cancer Synthetic Lethality in Cancer-Lessons Learnt from PARP Inhibitors.
Cancer Treat Res
; 186: 13-23, 2023.
Article
in En
| MEDLINE
| ID: mdl-37978128
ABSTRACT
PARP inhibitors now have proven utility in the treatment of homologous recombination (HR) defective cancers. These drugs, and the synthetic lethality effect they exploit, have not only taught us how to approach the treatment of HR defective cancers but have also illuminated how resistance to a synthetic lethal approach can occur, how cancer-associated synthetic lethal effects are perhaps more complex than we imagine, how the better use of biomarkers could improve the success of treatment and even how drug resistance might be targeted. Here, we discuss some of the lessons learnt from the study of PARP inhibitor synthetic lethality and how these lessons might have wider application. Specifically, we discuss the concept of synthetic lethal penetrance, phenocopy effects in cancer such as BRCAness, synthetic lethal resistance, the polygenic and complex nature of synthetic lethal interactions, how evolutionary double binds could be exploited in treatment as well as future horizons for the field.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Neoplasms
/
Antineoplastic Agents
Limits:
Humans
Language:
En
Journal:
Cancer Treat Res
Year:
2023
Document type:
Article
Affiliation country:
United kingdom