Fig. 2: Lactylation-mediated mechanisms of cancer cell death resistance.

This schematic illustrates how lactylation drives cancer cell death resistance through diverse mechanisms, encompassing both intrinsic cell survival pathways and extrinsic microenvironmental remodeling. A DNA Repair Enhancement. Lactylation augments DNA damage repair pathways to promote survival under genotoxic stress. B Ferroptosis Resistance. Lactylation coordinates metabolic rewiring to confer resistance to iron-dependent cell death. C Cuproptosis Resistance. Lactylation promotes resistance to copper-induced cell death. D Autophagy Enhancement. Lactylation promotes tumor adaptation by activating and sustaining autophagic flux. E Stemness Maintenance. Lactylation enforces a cancer stem-like cell state, underpinning therapy evasion. F Drug Efflux Upregulation. Lactylation drives the expression of efflux transporters, reducing intracellular drug accumulation. G PD-L1 Upregulation. Lactylation elevates PD-L1 levels through transcriptional and post-translational mechanisms, facilitating immune evasion. H Immune Cell Reprogramming. Lactylation induces pro-tumor phenotypic and functional shifts in immune cells while suppressing anti-tumor immunity. I Pathological Angiogenesis. Lactylation activates pro-angiogenic programs in both tumor and stromal cells to fuel tumor vascularization. Created in BioRender. Chengjiao Y (2026) https://BioRender.com/94mlfod.