Disease Information

General Information of the Disease (ID: DIS00528)

• Name: Liver cancer
• ICD: ICD-11: 2C12

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

Sorafenib

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Metabolic Reprogramming via Altered Pathways (MRAP)

Key Molecule: Activator of thyroid and retinoid receptors (ACTR) [1]

• Metabolic Type: Glucose metabolism
• Resistant Disease: Advanced hepatocellular carcinoma [ICD-11: 2C12.02]
• Resistant Drug: Sorafenib
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: ACTR KO HepG2 cells; Liver; Homo sapiens (Human); CVCL_0027
• In Vitro Model: ACTR KO HepG2 cells transiently transfected with ACTR; Liver; Homo sapiens (Human); CVCL_0027
• In Vitro Model: ACTR WT cells; Liver; Homo sapiens (Human); CVCL_4499
• In Vitro Model: Huh7 cells; Kidney; Homo sapiens (Human); CVCL_U442
• Experiment for Molecule Alteration: Gene expression profiles
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: ACTR promotes glycolysis through upregulation of glucose uptake, ATP and lactate production, and reduction of the extracellular acidification and the oxygen consumption rates. Glycolysis regulated by ACTR is vital for the susceptibility of HCC to sorafenib in vitro and in vivo.

Key Molecule: Activator of thyroid and retinoid receptors (ACTR) [1]

• Metabolic Type: Glucose metabolism
• Resistant Disease: Advanced hepatocellular carcinoma [ICD-11: 2C12.02]
• Resistant Drug: Sorafenib
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vivo Model: BALB/c nude mice, ACTR KO cells; BALB/c nude mice, ACTR WT cells; Mice
• Experiment for Molecule Alteration: Gene expression profiles
• Experiment for Drug Resistance: Tumor growth assay
• Mechanism Description: ACTR promotes glycolysis through upregulation of glucose uptake, ATP and lactate production, and reduction of the extracellular acidification and the oxygen consumption rates. Glycolysis regulated by ACTR is vital for the susceptibility of HCC to sorafenib in vitro and in vivo.

References

• Ref 1: Activator of thyroid and retinoid receptor increases sorafenib resistance in hepatocellular carcinoma by facilitating the Warburg effect. Cancer Sci. 2020 Jun;111(6):2028-2040.