Disease Information

General Information of the Disease (ID: DIS00535)

• Name: Breast cancer
• ICD: ICD-11: 2C60

Type(s) of Resistant Mechanism of This Disease

  MRAP: Metabolic Reprogramming via Altered Pathways

Drug Resistance Data Categorized by Drug

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

Endoxifen

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Metabolic Reprogramming via Altered Pathways (MRAP)

Key Molecule: AMP-activated kinase alpha-2 (PRKAA2) [1]

• Metabolic Type: Glucose metabolism
• Resistant Disease: Estrogen receptor (ER)-positive breast cancer [ICD-11: 2C60.6]
• Resistant Drug: Endoxifen
• Molecule Alteration: Autophosphorylation; T172
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: ER+ MCF7 BC cells; Breast; Homo sapiens (Human); CVCL_0031
• In Vitro Model: TRC cells; Breast; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: Cell viability assay
• Mechanism Description: Therefore, our results indicate increased activation of AKT and AMPK with metabolic reprogramming and increased autophagy in TAM-resistant cells. Simultaneous inhibition of AKT and FAO/autophagy is necessary to fully sensitize resistant cells to endoxifen.

Key Molecule: AKT serine/threonine kinase (AKT) [1]

• Metabolic Type: Glucose metabolism
• Resistant Disease: Estrogen receptor (ER)-positive breast cancer [ICD-11: 2C60.6]
• Resistant Drug: Endoxifen
• Molecule Alteration: Autophosphorylation; S473
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: ER+ MCF7 BC cells; Breast; Homo sapiens (Human); CVCL_0031
• In Vitro Model: TRC cells; Breast; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: Cell viability assay
• Mechanism Description: Therefore, our results indicate increased activation of AKT and AMPK with metabolic reprogramming and increased autophagy in TAM-resistant cells. Simultaneous inhibition of AKT and FAO/autophagy is necessary to fully sensitize resistant cells to endoxifen.

References

• Ref 1: Fatty acid oxidation and autophagy promote endoxifen resistance and counter the effect of AKT inhibition in ER-positive breast cancer cells. J Mol Cell Biol. 2021 Sep 11;13(6):433-444.