Disease Information

General Information of the Disease (ID: DIS00507)

• Name: Oesophagogastric cancer
• ICD: ICD-11: 2B71

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

Cisplatin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Metabolic Reprogramming via Altered Pathways (MRAP)

Key Molecule: Pyruvate dehydrogenase kinase 2 (PDK2) [1]

• Metabolic Type: Glucose metabolism
• Resistant Disease: Esophageal squamous cell carcinoma [ICD-11: 2B70.3]
• Resistant Drug: Cisplatin
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vivo Model: Male BALB/c nude mice (6-week old), with KYSE150 cells; Mice
• Experiment for Molecule Alteration: qRT-PCR; Western blot analysis
• Experiment for Drug Resistance: Tumor volume assay
• Mechanism Description: PDK1 inhibition by siRNA or DCA significantly suppressed the growth of ESCC cells. miR-6516-5p/PDK1 axis suppressed the growth of ESCC cell by inhibiting glycolysis. Moreover, DCA and DDP synergistically inhibited the progression and glycolysis ability of ESCC cells both in vitro and in vivo by increasing oxidative stress partly through the suppression of Keap1/Nrf2 signaling pathway.

Clinical Trial Drug(s) 1 drug(s) in total

Dichloroacetic acid

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Metabolic Reprogramming via Altered Pathways (MRAP)

Key Molecule: Pyruvate dehydrogenase kinase 2 (PDK2) [1]

• Metabolic Type: Glucose metabolism
• Sensitive Disease: Esophageal squamous cell carcinoma [ICD-11: 2B70.3]
• Sensitive Drug: Dichloroacetic acid
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vivo Model: Male BALB/c nude mice (6-week old), with KYSE150 cells; Mice
• Experiment for Molecule Alteration: qRT-PCR; Western blot analysis
• Experiment for Drug Resistance: Tumor volume assay
• Mechanism Description: PDK1 inhibition by siRNA or DCA significantly suppressed the growth of ESCC cells. miR-6516-5p/PDK1 axis suppressed the growth of ESCC cell by inhibiting glycolysis. Moreover, DCA and DDP synergistically inhibited the progression and glycolysis ability of ESCC cells both in vitro and in vivo by increasing oxidative stress partly through the suppression of Keap1/Nrf2 signaling pathway.

References

• Ref 1: PDK1 regulates the progression of esophageal squamous cell carcinoma through metabolic reprogramming. Mol Carcinog. 2023 Jun;62(6):866-881.