Importance of landscape exploration and progress in molecular therapies and precision medicine for pancreatic ductal adenocarcinoma

Table 4 Challenges and opportunities for recent targeted therapy options that have been approved and recommended by the Food and Drug Administration for treating pancreatic cancer

Targeted pathway	Frequency of mutation	Clinical phase	Targeted therapies approved by the FDA
KRAS [G12D, G12V, G12R, G12C, G13 (D, C, S, R)]	95%	Phase I-II	Sotorasib (AMG 510), adagrasib (MRTX849)
BRAF (V600E)	13.7%	Phase I-III	Dabrafenib, trametinib
NTRK fusion	0.3%	Phase II	Larotrectinib, entrectinib
NRG-1 fusion	0.5%	Phase I-II	Afatinib, zenocutuzumab
BRCA1/2/PALB2	3%	Phase I-III	Olaparib, cisplatin, niraparib
MSI-H/dMMR	4.7%	Phase I-II	Pembrolizumab
FGFR2	43%-69%	Phase II	Pemigatinib
MEK/ERK	1%	Phase II	Trametinib
RET fusion	1%	Phase II	Selpercatinib, pralsetinib (BLU-667)

FDA: United States Food and Drug Administration; KRAS: Kirsten rat sarcoma oncogene; BRAF: B-raf proto oncogene; NTRK: Neurotrophic receptor tyrosine kinase; NRG-1: Neuregulin-1; BRCA1/2: Breast cancer susceptibility gene 1/2; PALB2: Partner and localizer of breast cancer 2; MSI-H: Microsatellite instability high; dMMR: Mismatch repair deficient; FGFR2: Fibroblast growth factor receptor 2; MEK: Mitogen activated protein kinase; ERK: Extracellular signal regulated kinase; RET: Rearranged during transfection.