Disease Information

General Information of the Disease (ID: DIS00524)

• Name: Brain cancer
• ICD: ICD-11: 2A00

Type(s) of Resistant Mechanism of This Disease

  MRAP: Metabolic Reprogramming via Altered Pathways

Drug Resistance Data Categorized by Drug

Approved Drug(s) 1 drug(s) in total

Temozolomide

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Metabolic Reprogramming via Altered Pathways (MRAP)

Key Molecule: X-ray repair cross-complementing protein 1 (XRCC1) [1]

• Metabolic Type: Glucose metabolism
• Resistant Disease: Aldh1a3-overexpressing glioblastoma [ICD-11: 2A00.0]
• Resistant Drug: Temozolomide
• Molecule Alteration: Lactylation; K247
• Experimental Note: Identified from the Human Clinical Data
• In Vivo Model: Patients with GBM; Homo Sapiens
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: Survival after radiochemotherapy assay
• Mechanism Description: ALDH1A3-mediated tetramerization of PKM2 induces glycometabolic reprogramming in GSCs. Accumulation of lactate increases the lactylation of the K247 site on XRCC1. The lactylation of XRCC1 improves DNA repair via its increased nuclear localization. By blocking PKM2, D34-919 restores sensitivity to chemoradiotherapy for GBMs

Key Molecule: X-ray repair cross-complementing protein 1 (XRCC1) [1]

• Metabolic Type: Glucose metabolism
• Resistant Disease: Aldh1a3-overexpressing glioblastoma [ICD-11: 2A00.0]
• Resistant Drug: Temozolomide
• Molecule Alteration: Lactylation; K247
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Rescue cells; Brain; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: ALDH1A3-mediated tetramerization of PKM2 induces glycometabolic reprogramming in GSCs. Accumulation of lactate increases the lactylation of the K247 site on XRCC1. The lactylation of XRCC1 improves DNA repair via its increased nuclear localization. By blocking PKM2, D34-919 restores sensitivity to chemoradiotherapy for GBMs

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Metabolic Reprogramming via Altered Pathways (MRAP)

Key Molecule: X-ray repair cross-complementing protein 1 (XRCC1) [1]

• Metabolic Type: Glucose metabolism
• Sensitive Disease: Aldh1a3-overexpressing glioblastoma [ICD-11: 2A00.0]
• Sensitive Drug: Temozolomide
• Molecule Alteration: Lactylation; K247
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: ALDH1A3 knockout cells; Brain; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: ALDH1A3-mediated tetramerization of PKM2 induces glycometabolic reprogramming in GSCs. Accumulation of lactate increases the lactylation of the K247 site on XRCC1. The lactylation of XRCC1 improves DNA repair via its increased nuclear localization. By blocking PKM2, D34-919 restores sensitivity to chemoradiotherapy for GBMs

References

• Ref 1: Glycometabolic reprogramming-induced XRCC1 lactylation confers therapeutic resistance in ALDH1A3-overexpressing glioblastoma. Cell Metab. 2024 Aug 6;36(8):1696-1710.e10.