Table 2.

Combined therapeutic strategies targeting the glycolysis-lactylation axis.

Combination strategy	Representative agents	Mechanism of action	Model and efficacy
Metabolic Intervention + Radiotherapy	LDHA inhibitor (e.g., Stiripentol)	Induces ATP depletion and ROS accumulation, impairing DNA repair.	Enhances radiosensitivity in prostate cancer (110).
	Fluvastatin (MCT4 inhibitor)	Disrupts lactate export, induces metabolic stress	Enhances radiotherapy efficacy in lung adenocarcinoma (99).
Metabolic Intervention + Targeted Therapy	Stiripentol + Temozolomide	Inhibits LDHA/B & NBS1 lactylation, impairs DNA repair	Restores TMZ sensitivity in glioblastoma (47).
	Liposomal IGF2BP3 siRNA/2-DG + Lenvatinib	Inhibits IGF2BP2 lactylation, reversing metabolic reprogramming.	Restores lenvatinib sensitivity in hepatocellular carcinoma (54).
Metabolic Intervention + Immunotherapy	LDHA inhibitor + anti-PD-L1	Reduces lactate, remodels TME, reverses T cell exhaustion.	Synergistic tumor suppression in NSCLC models (46).
	pH-responsive AZD3965 nanodrug + anti-PD-L1	Enhances targeting, reduces toxicity, synergistically modulates TME	Improves efficacy and survival in mouse models (119).
Emerging Strategies	SIRT2 inhibitor (AGK2) + Copper ionophore	Inhibits METTL16 lactylation, enhancing cuproptosis sensitivity.	Synergistic effect in gastric cancer models (121).