title: Targeting deficient DNA damage repair in gastric cancer.
abstract: BACKGROUND
  Over recent years our understanding of DNA damage repair has evolved leading to an expansion of therapies attempting to exploit DNA damage repair deficiencies across multiple solid tumours. Gastric cancer has been identified as a tumour where a subgroup of patients demonstrates deficiencies in the homologous recombination pathway providing a potential novel treatment approach for this poor prognosis disease.
  
  
  METHODS
  This review provides an overview of DNA damage repair and how this has been targeted to date in other tumour types exploiting the concept of synthetic lethality. This is followed by a discussion of how deficiencies in homologous recombination may be identified across tumour types and on recent progress in targeting DNA repair deficiencies in gastric cancer.
  
  
  CONCLUSIONS
  Gastric cancer remains a difficult malignancy to treat and the possibility of targeting deficient DNA repair in a subgroup of patients is an exciting prospect. Future combinations with immunotherapy and radiotherapy are appealing and appear to have a sound biological rationale. However, much work remains to be done to understand the significance of the genetic and epigenetic alterations involved, to elucidate the optimum predictive signatures or biomarkers and to consider means of overcoming treatment resistance.
authors.affiliation: a Department of Medicine , The Royal Marsden NHS Foundation Trust, GI and Lymphoma Unit , Sutton , UK.
authors.forename: Kate
authors.initials: K
authors.lastname: Young
authors.affiliation: a Department of Medicine , The Royal Marsden NHS Foundation Trust, GI and Lymphoma Unit , Sutton , UK.
authors.forename: Naureen
authors.initials: N
authors.lastname: Starling
authors.affiliation: a Department of Medicine , The Royal Marsden NHS Foundation Trust, GI and Lymphoma Unit , Sutton , UK.
authors.forename: David
authors.initials: D
authors.lastname: Cunningham
mesh_terms: D004249:DNA Damage; D004260:DNA Repair; D059765:Homologous Recombination; D006801:Humans; D013274:Stomach Neoplasms / Q000628:therapy*
keywords: BRCAness; DNA damage repair; Gastric adenocarcinoma; PARP inhibitor; ataxia telangiectasia mutated (ATM); homologous recombination deficiency (HRD); synthetic lethality