Therapeutic pancreatic cancer biomarkers and pharmacogenetics

Abstract

FOLFIRINOX and gemcitabine plus nab-paclitaxel represent the most effective chemotherapy regimens for metastatic pancreatic cancer patients nowadays, but the median overall survival remains less than one year. Pharmacogenomics and the individualization of therapy represent a promising strategy, including identifying patients at increased risk of toxicity. This review summarizes contemporary knowledge about genetic variability and putative biomarkers with published associations to therapy responses of pancreatic cancer not only for gold standard treatment regimens (FOLFIRINOX, gemcitabine/nab-paclitaxel and nal-IRI/5-fluorouracil) but also for other therapeutic options regarding targeted therapy and immunotherapy. From the published data reviewed, it is evident that the problem is highly complex, and the ultimate profile of the drug-sensitive or resistant patient, followed by individualized therapy, is the most probable way to improve the poor prognosis of pancreatic cancer patients. Additionally, we will give a brief recap of what has been learned from genome-wide association studies, from gene candidate studies carried out in the context of large consortia such as the Pancreatic Disease Research (PANDoRA) consortium, and from studies focused on specific mutations in DNA repair genes.