Precision medicine advances in pancreatic cancer driven by genomic and molecular alterations

Table 1 Key genomic alterations in pancreatic ductal adenocarcinoma and associated targeted therapies

Gene/alteration	Prevalence in PDAC	Associated targeted therapy/clinical implication
KRAS (G12D, G12V, G12R)	Approximately 80%-90%	Allele-specific inhibitors under development; RNAi strategies in preclinical models
KRAS G12C	< 2%	Sotorasib, adagrasib (limited efficacy in PDAC)
BRCA1/2	Approximately 4%-7%	PARP inhibitors (e.g., olaparib); platinum-based chemotherapy
BRAF (V600)	< 1%	BRAF/MEK inhibitors (e.g., dabrafenib + trametinib; off-label use)
NTRK fusions	< 1%	TRK inhibitors (larotrectinib, entrectinib)
FGFR2 fusions	Rare	FGFR inhibitors (e.g., pemigatinib; in clinical trials)
RET fusions	Rare	RET inhibitors (e.g., selpercatinib; in clinical trials)
dMMR/MSI-H	< 2%	Immune checkpoint inhibitors (e.g., pembrolizumab)
High TMB	Rare	Potential responsiveness to ICIs
TP53/CDKN2A/SMAD4 (co-mutations)	> 50%	Prognostic markers; may influence resistance and response to combination therapies

KRAS: Kirsten rat sarcoma viral oncogene homolog; BRCA: Breast cancer susceptibility gene; BRAF: V-raf murine sarcoma viral oncogene homolog B1; NTRK: Neurotrophic receptor tyrosine kinase; FGFR: Fibroblast growth factor receptor; dMMR: Deficient mismatch repair; MSI-H: Microsatellite instability-high; TMB: Tumor mutational burden; TP53: Tumor protein p53; CDKN2A: Cyclin-dependent kinase inhibitor 2A; PDAC: Pancreatic ductal adenocarcinoma; RNAi: RNA interference; PARP: Poly(ADP-ribose) polymerase; MEK: Mitogen-activated protein kinase; TRK: Tropomyosin receptor kinase; ICIs: Immune checkpoint inhibitors.