Targeting the lysine lactylome for the treatment of glioma

Article Figures & Data

Download figure
Open in new tab
Download powerpoint
Figure 1
Mechanisms through which lactylation promotes tumorigenesis and chemotherapy resistance in glioma. Left, mechanism of regulation of gene expression through histone lactylation. Middle, XRCC1 lactylation enhances chemoradiotherapy resistance. Right, cGAS lactylation supports immune invasion in glioma.

Table 1

Influence of distinct histone lactylation sites on glioma progression

Histone lactylation site	Influence on glioma progression	Key findings
H3K9	Modulates immune suppression	H3K9 lactylation leads to upregulation of immunosuppressive cytokines and aids in immune evasion¹⁰.
H3K18	Promotes immune evasion	H3K18 lactylation enhances the expression of genes involved in tumor proliferation and suppresses immune responses⁸.
H3K27	Promotes tumor growth	H3K27 lactylation is associated with activation of oncogenes and suppression of tumor suppressor genes⁹.
H4K12	Supports stemness and tumorigenicity	H4K12 lactylation maintains glioma stem cell properties, and contributes to tumor initiation and resistance to therapy¹¹.

Table 2

Summary of crucial studies on lactylation targeting therapy in glioma

Target	Study	STAGE	Key findings
GLUT1	Li et al.¹⁸	Pre-clinical	Dual-regulation thermogels that inhibit lactate excretion and block PD-1/PD-L1 significantly enhance the efficacy of immunotherapy for glioblastoma.
HK2	Agnihotri et al.¹⁹	Phase 0/1 trial (NCT03763396)	Ketoconazole and posaconazole suppress GBM cell proliferation by decreasing glycolysis activity.
PKM2	Li et al.⁷	Pre-clinical	D34-919, a novel inhibitor of PKM2, reverses glycolysis reprogramming, decreases XRCC1 lactylation levels, and sensitizes glioblastoma to chemo-radiotherapy.
LDHA	Sun et al.¹²	Pre-clinical	Inhibition of LDHA by oxamate diminishes the immunosuppressive tumor microenvironment and enhances CAR-T cell therapy efficacy against glioblastoma.