Disease Information

General Information of the Disease (ID: DIS00522)

• 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) 2 drug(s) in total

Etoposide

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Metabolic Reprogramming via Altered Pathways (MRAP)

Key Molecule: Geranylgeranyl diphosphate synthase 1 (GGPS1) [1]

• Metabolic Type: Lipid metabolism
• Resistant Disease: Small cell lung carcinoma [ICD-11: 2C25.1]
• Resistant Drug: Etoposide
• Molecule Alteration: Expression; Up-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Lung cancer [ICD-11: 2C25]
• The Specified Disease: Small cell lung carcinoma
• The Studied Tissue: Lung tissue
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 3.06E-02; Fold-change: 8.03E-02; Z-score: 2.18E+00
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Biosynthesis of terpenoids and steroids; Activation; hsa01062
• Cell Pathway Regulation: Indole diterpene alkaloid biosynthesis; Activation; hsa00403
• In Vitro Model: DMS-114 cells; Lung; Homo sapiens (Human); CVCL_1174
• In Vitro Model: H146 cells; Lung; Homo sapiens (Human); CVCL_1473
• In Vitro Model: H209 cells; Lung; Homo sapiens (Human); CVCL_9V41
• In Vitro Model: H446 cells; Lung; Homo sapiens (Human); CVCL_1562
• In Vitro Model: H526 cells; Lung; Homo sapiens (Human); CVCL_1569
• In Vitro Model: H82 cells; Lung; Homo sapiens (Human); CVCL_1591
• Experiment for Molecule Alteration: qRT-PCR; Western blot analysis
• Experiment for Drug Resistance: Cell viability assay
• Mechanism Description: Mechanistically, statins induce oxidative stress accumulation and apoptosis through the GGPP synthase?1 (GGPS1)-RAB7A-autophagy axis. Statin treatment overcomes both intrinsic and acquired SCLC chemoresistance in vivo across different SCLC PDX models bearing high GGPS1 levels. Moreover, we show that GGPS1 expression is negatively associated with survival in patients with SCLC

Cisplatin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Metabolic Reprogramming via Altered Pathways (MRAP)

Key Molecule: Geranylgeranyl diphosphate synthase 1 (GGPS1) [1]

• Metabolic Type: Lipid metabolism
• Resistant Disease: Small cell lung carcinoma [ICD-11: 2C25.1]
• Resistant Drug: Cisplatin
• 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
• The Studied Tissue: Lung tissue
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 7.06E-20; Fold-change: 4.40E-02; Z-score: 9.57E+00
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Biosynthesis of terpenoids and steroids; Activation; hsa01062
• Cell Pathway Regulation: Indole diterpene alkaloid biosynthesis; Activation; hsa00403
• In Vitro Model: DMS-114 cells; Lung; Homo sapiens (Human); CVCL_1174
• In Vitro Model: H146 cells; Lung; Homo sapiens (Human); CVCL_1473
• In Vitro Model: H209 cells; Lung; Homo sapiens (Human); CVCL_9V41
• In Vitro Model: H446 cells; Lung; Homo sapiens (Human); CVCL_1562
• In Vitro Model: H526 cells; Lung; Homo sapiens (Human); CVCL_1569
• In Vitro Model: H82 cells; Lung; Homo sapiens (Human); CVCL_1591
• Experiment for Molecule Alteration: qRT-PCR; Western blot analysis
• Experiment for Drug Resistance: Cell viability assay
• Mechanism Description: Mechanistically, statins induce oxidative stress accumulation and apoptosis through the GGPP synthase?1 (GGPS1)-RAB7A-autophagy axis. Statin treatment overcomes both intrinsic and acquired SCLC chemoresistance in vivo across different SCLC PDX models bearing high GGPS1 levels. Moreover, we show that GGPS1 expression is negatively associated with survival in patients with SCLC

References

• Ref 1: Ceramide kinase confers tamoxifen resistance in estrogen receptor-positive breast cancer by altering sphingolipid metabolism. Pharmacol Res. 2023 Jan;187:106558.