Genomic instability in pancreatic adenocarcinoma: a new step towards precision medicine and novel therapeutic approaches

Ibrahim H. Sahin, Maeve A. Lowery, Zsofia K. Stadler, Erin Salo-Mullen, Christine A. Iacobuzio-Donahue, David P. Kelsen, Eileen M. O’Reilly

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)1-13
Number of pages13
JournalExpert Review of Gastroenterology and Hepatology
DOIs
StateAccepted/In press - Feb 27 2016
Externally publishedYes

Fingerprint

Precision Medicine
Genomic Instability
Pancreatic Neoplasms
Adenocarcinoma
Genome
DNA Repair
Neoplasms
DNA Fingerprinting
Germ-Line Mutation
DNA
Therapeutics
Platinum
DNA Damage
Biomarkers
Poly(ADP-ribose) Polymerase Inhibitors

Keywords

  • ARID1
  • ATM
  • BRCA1
  • BRCA2
  • cisplatin
  • DNA repair
  • genomic instability
  • MSH
  • PALB2
  • Pancreatic cancer
  • PARP inhibitors
  • PARP1
  • synthetic lethality

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

Cite this

Sahin, I. H., Lowery, M. A., Stadler, Z. K., Salo-Mullen, E., Iacobuzio-Donahue, C. A., Kelsen, D. P., & O’Reilly, E. M. (Accepted/In press). Genomic instability in pancreatic adenocarcinoma: a new step towards precision medicine and novel therapeutic approaches. Expert Review of Gastroenterology and Hepatology, 1-13. https://doi.org/10.1586/17474124.2016.1153424

Genomic instability in pancreatic adenocarcinoma : a new step towards precision medicine and novel therapeutic approaches. / Sahin, Ibrahim H.; Lowery, Maeve A.; Stadler, Zsofia K.; Salo-Mullen, Erin; Iacobuzio-Donahue, Christine A.; Kelsen, David P.; O’Reilly, Eileen M.

In: Expert Review of Gastroenterology and Hepatology, 27.02.2016, p. 1-13.

Research output: Contribution to journalArticle

Sahin, Ibrahim H. ; Lowery, Maeve A. ; Stadler, Zsofia K. ; Salo-Mullen, Erin ; Iacobuzio-Donahue, Christine A. ; Kelsen, David P. ; O’Reilly, Eileen M. / Genomic instability in pancreatic adenocarcinoma : a new step towards precision medicine and novel therapeutic approaches. In: Expert Review of Gastroenterology and Hepatology. 2016 ; pp. 1-13.
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