Disease Information

General Information of the Disease (ID: DIS00525)

• Name: Lung cancer
• ICD: ICD-11: 2C25

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

Pemetrexed

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Metabolic Reprogramming via Altered Pathways (MRAP)

Key Molecule: Aldo-keto reductase family 1 member B10 (AKR1B10) [1]

• Metabolic Type: Glucose metabolism
• Sensitive Disease: Lung cancer brain metastasis [ICD-11: 2C25.3]
• Sensitive Drug: Pemetrexed
• Molecule Alteration: Expression; Up-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Lung cancer [ICD-11: 2C25]
• The Specified Disease: Lung cancer brain metastasis
• The Studied Tissue: Lung tissue
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 1.92E-01; Fold-change: 2.98E-01; Z-score: 1.31E+00
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: AKR1B10 knockdown PC9-BrM3 cells; Lung; Homo sapiens (Human); CVCL_XA19
• Experiment for Drug Resistance: Cell viability assay; Clonogenicity assay; Cell apoptosis assay
• Mechanism Description: Metabolic profiling revealed that AKR1B10 prominently facilitated the Warburg metabolism characterized by the overproduction of lactate. Glycolysis regulated by AKR1B10 is vital for the resistance to PEM. In mechanism, AKR1B10 promoted glycolysis by regulating the expression of lactate dehydrogenase (LDHA) and the increased lactate, acts as a precursor that stimulates histone lactylation (H4K12la), activated the transcription of CCNB1 and accelerated the DNA replication and cell cycle.

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Metabolic Reprogramming via Altered Pathways (MRAP)

Key Molecule: Aldo-keto reductase family 1 member B10 (AKR1B10) [1]

• Metabolic Type: Glucose metabolism
• Resistant Disease: Lung cancer brain metastasis [ICD-11: 2C25.3]
• Resistant Drug: Pemetrexed
• Molecule Alteration: Expression; Up-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Lung cancer [ICD-11: 2C25]
• The Specified Disease: Lung cancer brain metastasis
• The Studied Tissue: Lung tissue
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 1.92E-01; Fold-change: 2.98E-01; Z-score: 1.31E+00
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Highly brain metastatic lung cancer PC9-BrM3 cells; Lung; Homo sapiens (Human); CVCL_XA19
• Experiment for Drug Resistance: Cell viability assay; Cell colony formation assay
• Mechanism Description: Metabolic profiling revealed that AKR1B10 prominently facilitated the Warburg metabolism characterized by the overproduction of lactate. Glycolysis regulated by AKR1B10 is vital for the resistance to PEM. In mechanism, AKR1B10 promoted glycolysis by regulating the expression of lactate dehydrogenase (LDHA) and the increased lactate, acts as a precursor that stimulates histone lactylation (H4K12la), activated the transcription of CCNB1 and accelerated the DNA replication and cell cycle.

References

• Ref 1: Warburg effect enhanced by AKR1B10 promotes acquired resistance to pemetrexed in lung cancer-derived brain metastasis. J Transl Med. 2023 Aug 16;21(1):547.