Pharmacogenetics of treatments for pancreatic cancer

Expert Opin Drug Metab Toxicol. 2019 Jun;15(6):437-447. doi: 10.1080/17425255.2019.1620731. Epub 2019 May 24.


Introduction: Despite clinical efforts, pancreatic ductal adenocarcinoma (PDAC) has a dismal prognosis. The scarcity of effective therapies can be reflected by the lack of reliable biomarkers to adapt anticancer drugs prescription to tumors' and patients' features. Areas covered: Pharmacogenetics should provide the way to select patients who may benefit from a specific therapy that best matches individual and tumor genetic profile, but it has not yet led to gains in outcome. This review describes PDAC pharmacogenetics findings, critically reappraising studies on polymorphisms and -omics profiles correlated to response to gemcitabine, FOLFIRINOX, and nab-paclitaxel combinations, as well as limitations of targeted therapies. Further, we question whether personalized approaches will benefit patients to any significant degree, supporting the need of new strategies within well-designed trials and validated genomic tests for treatment decision-making. Expert opinion: A major challenge in PDAC is the identification of subgroups of patients who will benefit from treatments. Minimally-invasive tests to analyze biomarkers of drug sensitivity/toxicity should be developed alongside anticancer treatments. However, progress might fall below expectations because of tumor heterogeneity and clonal evolution. Whole-genome sequencing and liquid biopsies, as well as prospective validation in selected cohorts, should overcome the limitations of traditional pharmacogenetic approaches.

Keywords: FOLFIRINOX; Pancreatic cancer; gemcitabine; nab-paclitaxel; pharmacogenetic studies; promises and pitfalls of pharmacogenetic approaches; validated tests and clinical trials.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Biomarkers, Tumor / metabolism
  • Carcinoma, Pancreatic Ductal / drug therapy*
  • Carcinoma, Pancreatic Ductal / genetics
  • Carcinoma, Pancreatic Ductal / pathology
  • Humans
  • Pancreatic Neoplasms / drug therapy*
  • Pancreatic Neoplasms / genetics
  • Pancreatic Neoplasms / pathology
  • Patient Selection
  • Pharmacogenetics / methods*
  • Prognosis


  • Biomarkers, Tumor