Therapeutic pancreatic cancer biomarkers and pharmacogenetics

Area of Science:

• Oncology
• Pharmacogenomics
• Translational Medicine

Background:

• Metastatic pancreatic cancer has a poor prognosis, with current chemotherapies like FOLFIRINOX offering limited survival benefits.
• Identifying genetic factors influencing treatment response and toxicity is crucial for improving patient outcomes.
• Pharmacogenomics offers a promising avenue for personalizing pancreatic cancer therapy.

Purpose of the Study:

• To review current knowledge on genetic variability and biomarkers associated with treatment response in pancreatic cancer.
• To explore pharmacogenomic associations for standard regimens (FOLFIRINOX, gemcitabine/nab-paclitaxel, nal-IRI/5-FU), targeted therapies, and immunotherapies.
• To summarize findings from genome-wide association studies and specific gene mutation analyses.

Main Methods:

• Comprehensive literature review of published data on pharmacogenomics and pancreatic cancer treatment.
• Analysis of genetic variability and biomarker associations with response to various therapeutic regimens.
• Inclusion of data from large consortia like PANDoRA and studies on DNA repair gene mutations.

Main Results:

• The complexity of pancreatic cancer treatment response is evident, influenced by numerous genetic factors.
• Published data highlight associations between genetic variability and response to FOLFIRINOX, gemcitabine/nab-paclitaxel, and other treatments.
• Studies indicate that genetic profiling is essential for predicting drug sensitivity and resistance.

Conclusions:

• Individualized therapy based on a patient's genetic profile is the most promising strategy to improve pancreatic cancer survival.
• Pharmacogenomic insights are vital for optimizing treatment selection and minimizing toxicity.
• Further research, including genome-wide and gene-specific studies, is needed to fully realize personalized medicine in pancreatic cancer.