The landscape of pancreatic cancer therapeutic resistance mechanisms

Saswati Chand, Kevin O’Hayer, Fernando F. Blanco, Jordan M. Winter, Jonathan R. Brody

Research output: Contribution to journalReview articlepeer-review

61 Scopus citations

Abstract

Pancreatic cancer (pancreatic ductal adenocarcinoma, PDA) is infamously moving to the top of the list as one of the most lethal cancers with an overall 5 year survival rate of 7%. Multiple genomic- based and molecular characterization studies of PDA specimens and established animal models have provided the field with multiple targets and a progression model of this disease. Still, to date, the best therapeutic options are surgery and combination cytotoxic therapies. In general, even in the best case scenario (i.e., an early stage diagnosis and a response to a specific therapy), most of these fortunate patients’ PDA cells acquire or exert resistance mechanisms and eventually kill the patient. Herein, we touch on a growing field of investigation that focuses on PDA cell therapeutic resistance mechanisms. We examine extrinsic elements (i.e., the tumor microenvironment, hypoxia) to the intrinsic processes within the cell (i.e., post-transcriptional gene regulation and somatic mutations) that are important for therapeutic efficacy and resistance. Even as better targeted and personalized approaches move through the clinical trial pipeline the discussed resistance mechanisms will most likely play a role in the management of this deadly disease.

Original languageEnglish (US)
Pages (from-to)273-283
Number of pages11
JournalInternational Journal of Biological Sciences
Volume12
Issue number3
DOIs
StatePublished - Jan 27 2016
Externally publishedYes

Keywords

  • Chemotherapeutic resistance
  • DNA damage
  • HuR
  • Hypoxia
  • Pancreatic ductal adenocarcinoma

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Applied Microbiology and Biotechnology
  • Molecular Biology
  • Developmental Biology
  • Cell Biology

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