Genomic instability in pancreatic adenocarcinoma: A new step towards precision medicine and novel therapeutic approaches Journal Article

   

Authors:	Sahin, I. H.; Lowery, M. A.; Stadler, Z. K.; Salo-Mullen, E.; Iacobuzio-Donahue, C. A.; Kelsen, D. P.; O'Reilly, E. M.
Article Title:	Genomic instability in pancreatic adenocarcinoma: A new step towards precision medicine and novel therapeutic approaches
Abstract:	Pancreatic cancer is one of the most challenging cancers. Whole genome sequencing studies have been conducted to elucidate the underlying fundamentals underscoring disease behavior. Studies have identified a subgroup of pancreatic cancer patients with distinct molecular and clinical features. Genetic fingerprinting of these tumors is consistent with an unstable genome and defective DNA repair pathways, which creates unique susceptibility to agents inducing DNA damage. BRCA1/2 mutations, both germline and somatic, which lead to impaired DNA repair, are found to be important biomarkers of genomic instability as well as of response to DNA damaging agents. Recent studies have elucidated that PARP inhibitors and platinum agents may be effective to induce tumor regression in solid tumors bearing an unstable genome including pancreatic cancer. In this review we discuss the characteristics of genomic instability in pancreatic cancer along with its clinical implications and the utility of DNA targeting agents particularly PARP inhibitors as a novel treatment approach.
Keywords:	cisplatin; homologous recombination; dna repair; genomic instability; microsatellite instability; pancreatic cancer; brca1; brca2; double-strand breaks; atm; colorectal-cancer; synthetic lethality; palb2; dna-damage response; poly(adp-ribose) polymerase; brca mutation carriers; ovarian carcinomas; parp inhibitors; cisplatin resistance; parp1; arid1; msh; combined inhibition
Journal Title:	Expert Review of Gastroenterology and Hepatology
Volume:	10
Issue:	8
ISSN:	1747-4124
Publisher:	Informa Healthcare
Date Published:	2016-01-01
Start Page:	893
End Page:	905
Language:	English
ACCESSION:	WOS:000381319000004
DOI:	10.1586/17474124.2016.1153424
PROVIDER:	wos
PMCID:	PMC4988832
PUBMED:	26881472
Notes:	Review -- Source: Wos

https://synapse.mskcc.org/synapse/works/has_related_data_chk/98720