Approaches for Identifying Novel Targets in Precision Medicine: Lessons from DNA Repair.
Adv Exp Med Biol
; 1007: 1-16, 2017.
Article
in En
| MEDLINE
| ID: mdl-28840549
ABSTRACT
Genome stability is maintained by a number of elegant mechanisms, which sense and repair damaged DNA. Germline defects that compromise genomic integrity result in cancer predisposition, exemplified by rare syndromes caused by mutations in certain DNA repair genes. These individuals often exhibit other symptoms including progeria and neurodegeneration. Paradoxically, some of these deleterious genetic alterations provide novel therapeutic opportunities to target cancer cells; an excellent example of such an approach being the recent development of poly (ADP-ribose) polymerase inhibitors as the first 'synthetic lethal' medicine for patients with BRCA-mutant cancers. The therapeutic exploitation of synthetic lethal interactions has enabled a novel approach to personalised medicine based on continued molecular profiling of patient and tumour material. This profiling may also aid clinicians in the identification of specific drug resistance mechanisms following relapse, and enable appropriate modification of the therapeutic regimen. This chapter focuses on therapeutic strategies designed to target aspects of the DNA damage response, and examines emerging themes demonstrating mechanistic overlap between DNA repair and neurodegeneration.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
DNA Damage
/
DNA Repair
/
Precision Medicine
/
Poly(ADP-ribose) Polymerase Inhibitors
Limits:
Female
/
Humans
/
Male
Language:
En
Journal:
Adv Exp Med Biol
Year:
2017
Document type:
Article
Affiliation country:
United kingdom