Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10895587 | Biochimica et Biophysica Acta (BBA) - Reviews on Cancer | 2014 | 10 Pages |
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.
Keywords
DSBPDACDNA-PK catalytic subunitPoly-ADP-ribose-polymeraseFOLFIRINOXDOT1LDNA-PKcsTIMSSBChk1TDPMMR5-FUATRDDRPARPNHEJBERVCPNERMdm2PFsPancreatic ductal adenocarcinomacheckpoint kinase 1TIMELESSprogression-free survivaloverall survivalnucleotide excision repairmismatch repairbase excision repairmurine double minute 2NSCLCNon-small cell lung cancerdouble strand breaksingle-strand breaknon-homologous end joiningDNA damaging agents5-fluorouracilHomologous recombinationChemoresistance
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Authors
Elaina N. Maginn, Camila H. de Sousa, Harpreet S. Wasan, Euan A. Stronach,