Disease Information

General Information of the Disease (ID: DIS00530)

• Name: Breast invasive carcinoma
• ICD: ICD-11: 2C61

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

Doxorubicin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Metabolic Reprogramming via Altered Pathways (MRAP)

Key Molecule: Pyruvate dehydrogenase (PDH) [1]

• Metabolic Type: Glucose metabolism
• Resistant Disease: Mammary carcinoma [ICD-11: 2C61.1]
• Resistant Drug: Doxorubicin
• Molecule Alteration: Phosphorylation; tyrosine-289
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: 4T1 cells expressing WT; Breast; Mus musculus (Mouse); CVCL_0125
• In Vitro Model: 4T1 cells expressing Y289F PDHA1; Breast; Mus musculus (Mouse); CVCL_0125
• Experiment for Drug Resistance: Cell viability assay
• Mechanism Description: The results suggest that Src contributes to the Warburg phenotype by inactivating PDH through tyrosine phosphorylation, and the metabolic effect of Src is essential for Src-driven malignancy and therapy resistance. Combination therapies consisting of both Src inhibitors and pro-oxidants may improve anticancer efficacy.

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

Saracatinib

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Metabolic Reprogramming via Altered Pathways (MRAP)

Key Molecule: Pyruvate dehydrogenase (PDH) [1]

• Metabolic Type: Glucose metabolism
• Resistant Disease: Mammary carcinoma [ICD-11: 2C61.1]
• Resistant Drug: Saracatinib
• Molecule Alteration: Phosphorylation; tyrosine-289
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: 4T1 mammary carcinoma cells; Breast; Mus musculus (Mouse); CVCL_0125
• Mechanism Description: The results suggest that Src contributes to the Warburg phenotype by inactivating PDH through tyrosine phosphorylation, and the metabolic effect of Src is essential for Src-driven malignancy and therapy resistance. Combination therapies consisting of both Src inhibitors and pro-oxidants may improve anticancer efficacy.

References

• Ref 1: Src drives the Warburg effect and therapy resistance by inactivating pyruvate dehydrogenase through tyrosine-289 phosphorylation. Oncotarget. 2016 May 3;7(18):25113-24.