DNA repair, overview

John Henry Barbe, Kevin M. O'Hayer, Jonathan R. Brody

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Pancreatic ductal adenocarcinoma (PDA) is a lethal disease with a five-year survival rate of approximately 5%. Any hope for long-term survival hinges on tumor resectability; however, less than 15% of PDA cases are operable. One of the differentiating factors of PDA is its ability to form micrometastases early in tumor growth, preventing surgery from being wholly effective in treating the cancer (Kelly KJ, Wong J, Gladdy R, Moore-Dalal K, Woo Y, Gonen M, et al., Ann Surg Oncol 16(12):3333-9, 2009). Moreover, there have been few advances in the treatment of metastatic disease in recent years. Newer cytotoxic treatments such as gemcitabine/nab-paclitaxel and FOLFIRINOX have made only marginal improvements in the quality of life and overall survival. Because of the overall poor prognosis and paucity of treatment options, there is a strong need for the development of new therapeutic targets and treatment modalities. Multiple recent studies have demonstrated the dysregulation of DNA repair mechanisms in PDA cells (Helleday T, Mol Oncol 5(4):387-93, 2011). Herein, we use PDA as a model tumor system in which to provide a thorough review of DNA repair mechanisms involved in cancer and how they may be targeted to generate novel therapeutics and potential cancer treatments (Table 1). We will review the exciting notion that although DNA repair defects may set the stage for tumorigenesis (prognostic marker), it also may be an Achilles heel of cancer cells that can be targeted (predictive marker). Specifically, targeting the DNA repair pathway in combination with traditional DNA damaging chemotherapeutics may lead to synergy and hopefully to better patient outcomes.

Original languageEnglish (US)
Title of host publicationCancer Therapeutic Targets
PublisherSpringer New York
Pages693-705
Number of pages13
Volume2-2
ISBN (Electronic)9781441907172
ISBN (Print)9781441907165
DOIs
StatePublished - Jan 1 2017
Externally publishedYes

Keywords

  • DNA repair defects and cancer
  • DNA-protein kinase catalytic subunits
  • Doublestrand break damage
  • ELAVL1
  • Fanconi anemia
  • Homologous repair
  • Human antigen R
  • Immunohistochemistry
  • Ku proteins
  • miRNAs
  • Non-homologous end joining
  • Nucleotide excision repair
  • Poly (ADP-ribose) polymerase (PARP) inhibition
  • Synthetic lethality

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

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