Lactylation in pancreatic cancer: From molecular mechanisms to therapeutic perspectives

Table 1 Key lactylation sites and their functional roles in cancer

Lactylated substrate	Cancer type	Functional consequence	Ref.
Histone H3K18	PDAC, breast cancer	Drives expression of MYC, vascular endothelial growth factor A, and pancreatic progenitor genes (PDX1, MNX1); promotes lineage plasticity	Yang et al[13], Lee et al[19], Wang et al[23]
Histone H3K9	Hepatocellular carcinoma	Activates programmed death 1 transcription, fostering immune evasion	Liu et al[14], Li et al[24]
PKM2	Colorectal cancer	Inhibits PKM2 activity, diverting glycolytic flux toward the pentose-phosphate pathway	Chen et al[16]
Breast cancer type 1 susceptibility protein (K1402)	PDAC (gemcitabine-resistant)	Enhances DNA-binding affinity, accelerates HR repair, promoting chemoresistance	Wang et al[20], Li et al[25]
RAD51 (K70)	PDAC (gemcitabine-resistant)	Enhances DNA-binding affinity, accelerates HR repair, promoting chemoresistance	Wang et al[20], Li et al[25]

It summarizes significant lactylation targets, their associated cancer contexts, and the functional consequences discussed above. HR: Homologous-recombination; PDAC: Pancreatic ductal adenocarcinoma; PKM2: Pyruvate kinase M2.