Advances in pancreatic cancer epigenetics: From the mechanism to the clinic

Table 5 Epigenetic therapeutic strategies in pancreatic cancer

Strategy	Targeted epigenetic mechanism	Therapeutic agents	Studies/efficacy
DNA demethylation	DNA methylation	5-Azacytidine (5-Aza), Decitabine	Used to restore silenced tumor suppressor genes. Clinical trials have shown limited success in PDAC
Histone deacetylation inhibition	Histone modification	Vorinostat, Romidepsin	Inhibits HDACs, leading to tumor suppressor gene activation and reduced tumor growth. Promising in early trials
miRNA therapy	Noncoding RNA	ExomiR-34a (miR-34a encapsulated in exosomes)	ExomiR-34a showed suppression of pancreatic cancer cell growth and induced apoptosis in preclinical trials
lncRNA modulation	Noncoding RNA	Antisense oligonucleotides, RNAi	Targets lncRNAs to reverse drug resistance and regulate oncogenes. Emerging as a promising approach
CRISPR/Cas13 for lncRNA	Noncoding RNA	CRISPR-Cas13	Modulates lncRNAs to target pancreatic cancer growth and metastasis. Still in preclinical stages
Combination therapy with immunotherapy	Epigenetic Modifications & Immunotherapy	HDAC inhibitors + PD-1/PD-L1 inhibitors	Epigenetic inhibitors combined with immune checkpoint inhibitors showed potential in enhancing immune responses

PDAC: Pancreatic ductal adenocarcinoma; lncRNA: Long noncoding RNA.