Disease Information

General Information of the Disease (ID: DIS00532)

• 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

Approved Drug(s) 1 drug(s) in total

Trastuzumab

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Metabolic Reprogramming via Altered Pathways (MRAP)

Key Molecule: NADH dehydrogenase 1 alpha subcomplex subunit 4-like 2 (NDUFA4L2) [1]

• Metabolic Type: Redox metabolism
• Resistant Disease: HER2-positive breast cancer [ICD-11: 2C60.8]
• Resistant Drug: Trastuzumab
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• In Vivo Model: NDUFA4L2-positive patients; Homo Sapiens
• Experiment for Molecule Alteration: Whole-transcriptome expression array
• Experiment for Drug Resistance: Hazard ratio assay
• Mechanism Description: Mechanistically, overexpression of NDUFA4L2 facilitated mitochondrial relocalization of HER2 and suppressed ROS production, thus rendering cancer cells more resistant to trastuzumab treatment.

Key Molecule: NADH dehydrogenase 1 alpha subcomplex subunit 4-like 2 (NDUFA4L2) [1]

• Metabolic Type: Redox metabolism
• Resistant Disease: HER2-positive breast cancer [ICD-11: 2C60.8]
• Resistant Drug: Trastuzumab
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• In Vivo Model: NDUFA4L2-negative patients; Homo Sapiens
• Experiment for Molecule Alteration: Whole-transcriptome expression array
• Experiment for Drug Resistance: Hazard ratio assay
• Mechanism Description: Mechanistically, overexpression of NDUFA4L2 facilitated mitochondrial relocalization of HER2 and suppressed ROS production, thus rendering cancer cells more resistant to trastuzumab treatment.

Key Molecule: NADH dehydrogenase 1 alpha subcomplex subunit 4-like 2 (NDUFA4L2) [1]

• Metabolic Type: Redox metabolism
• Resistant Disease: HER2-positive breast cancer [ICD-11: 2C60.8]
• Resistant Drug: Trastuzumab
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: BT-474 cells; Breast; Homo sapiens (Human); CVCL_0179
• In Vitro Model: BT474 cells; Breast; Homo sapiens (Human); CVCL_0179
• In Vitro Model: SK-BR-3 cells; Pleural effusion; Homo sapiens (Human); CVCL_0033
• In Vitro Model: Parental cells; Breast; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: Whole-transcriptome expression array
• Experiment for Drug Resistance: Cell viability assay
• Mechanism Description: Mechanistically, overexpression of NDUFA4L2 facilitated mitochondrial relocalization of HER2 and suppressed ROS production, thus rendering cancer cells more resistant to trastuzumab treatment.

References

• Ref 1: NDUFA4L2 promotes trastuzumab resistance in HER2-positive breast cancer. Ther Adv Med Oncol. 2021 Jun 30;13:17588359211027836.