title: Opportunities for translation: targeting DNA repair pathways in pancreatic cancer.
abstract: Pancreatic ductal adenocarcinoma (PDAC) remains one of the poorest prognosis neoplasms. It is typified by high levels of genomic aberrations and copy-number variation, intra-tumoural heterogeneity and resistance to conventional chemotherapy. Improved therapeutic options, ideally targeted against cancer-specific biological mechanisms, are urgently needed. Although induction of DNA damage and/or modulation of DNA damage response pathways are associated with the activity of a number of conventional PDAC chemotherapies, the effectiveness of this approach in the treatment of PDAC has not been comprehensively reviewed. Here, we review chemotherapeutic agents that have shown anti-cancer activity in PDAC and whose mechanisms of action involve modulation of DNA repair pathways. In addition, we highlight novel potential targets within these pathways based on the emerging understanding of PDAC biology and their exploitation as targets in other cancers.
authors.affiliation: Molecular Therapy Laboratory, Department of Cancer and Surgery, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 0NN, United Kingdom. Electronic address: e.maginn@imperial.ac.uk.
authors.forename: Elaina N
authors.initials: EN
authors.lastname: Maginn
authors.affiliation: Molecular Therapy Laboratory, Department of Cancer and Surgery, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 0NN, United Kingdom.
authors.forename: Camila H
authors.initials: CH
authors.lastname: de Sousa
authors.affiliation: Molecular Therapy Laboratory, Department of Cancer and Surgery, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 0NN, United Kingdom.
authors.forename: Harpreet S
authors.initials: HS
authors.lastname: Wasan
authors.affiliation: Molecular Therapy Laboratory, Department of Cancer and Surgery, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 0NN, United Kingdom.
authors.forename: Euan A
authors.initials: EA
authors.lastname: Stronach
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics / Q000628:therapy*; D056915:DNA Copy Number Variations; D004249:DNA Damage; D004260:DNA Repair / Q000187:drug effects / Q000235:genetics; D006801:Humans; D058990:Molecular Targeted Therapy / Q000379:methods*; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000628:therapy*; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D057170:Translational Research, Biomedical
chemical_list: D000970:Antineoplastic Agents
keywords: Chemoresistance; DNA damage response and repair; DNA damaging agents; Pancreatic ductal adenocarcinoma