Disease Information

General Information of the Disease (ID: DIS00523)

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

Type(s) of Resistant Mechanism of This Disease

  MRAP: Metabolic Reprogramming via Altered Pathways

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Drug

Approved Drug(s) 2 drug(s) in total

Fulvestrant

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Estrogen receptor alpha (ESR1) [1]

• Resistant Disease: Triple-negative breast cancer [ICD-11: 2C60.9]
• Resistant Drug: Fulvestrant
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: EGFR/HER2 signaling pathway; Regulation; N.A.
• In Vitro Model: MCF7 (Ful-R) cells; Breast; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: qRT-PCR
• Mechanism Description: In this study, we investigated the molecular mechanism underlying the loss of ER, FOXO3a, and induction of HER2 in fulvestrant-resistant breast cancer. Short-term fulvestrant treatment degraded ER proteins via the ubiquitin-proteasome degradation pathway in MCF7 cells. MCF7 cells turn into highly proliferative cells (fulvestrant-resistant cells: Ful-R) after long-term fulvestrant treatment. These cells exhibit markedly suppressed estrogen and progesterone receptor levels. The phosphorylation of EGFR, HER2, and ERK was induced in Ful-R, and these phosphorylation inhibitors suppressed cell proliferation in Ful-R.

Key Molecule: Mitogen-activated protein kinase (MAPK) [1]

• Resistant Disease: Triple-negative breast cancer [ICD-11: 2C60.9]
• Resistant Drug: Fulvestrant
• Molecule Alteration: Phosphorylation; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: EGFR/HER2 signaling pathway; Regulation; N.A.
• In Vitro Model: MCF7 (Ful-R) cells; Breast; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: Western blot assay
• Mechanism Description: In this study, we investigated the molecular mechanism underlying the loss of ER, FOXO3a, and induction of HER2 in fulvestrant-resistant breast cancer. Short-term fulvestrant treatment degraded ER proteins via the ubiquitin-proteasome degradation pathway in MCF7 cells. MCF7 cells turn into highly proliferative cells (fulvestrant-resistant cells: Ful-R) after long-term fulvestrant treatment. These cells exhibit markedly suppressed estrogen and progesterone receptor levels. The phosphorylation of EGFR, HER2, and ERK was induced in Ful-R, and these phosphorylation inhibitors suppressed cell proliferation in Ful-R.

Key Molecule: Progesterone receptor (PGR) [1]

• Resistant Disease: Triple-negative breast cancer [ICD-11: 2C60.9]
• Resistant Drug: Fulvestrant
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: EGFR/HER2 signaling pathway; Regulation; N.A.
• In Vitro Model: MCF7 (Ful-R) cells; Breast; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: qRT-PCR
• Mechanism Description: In this study, we investigated the molecular mechanism underlying the loss of ER, FOXO3a, and induction of HER2 in fulvestrant-resistant breast cancer. Short-term fulvestrant treatment degraded ER proteins via the ubiquitin-proteasome degradation pathway in MCF7 cells. MCF7 cells turn into highly proliferative cells (fulvestrant-resistant cells: Ful-R) after long-term fulvestrant treatment. These cells exhibit markedly suppressed estrogen and progesterone receptor levels. The phosphorylation of EGFR, HER2, and ERK was induced in Ful-R, and these phosphorylation inhibitors suppressed cell proliferation in Ful-R.

Key Molecule: Oncogenic epidermal growth factor receptor (EGFR) [1]

• Resistant Disease: Triple-negative breast cancer [ICD-11: 2C60.9]
• Resistant Drug: Fulvestrant
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: EGFR/HER2 signaling pathway; Regulation; N.A.
• In Vitro Model: MCF7 (Ful-R) cells; Breast; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: Western blot assay
• Mechanism Description: In this study, we investigated the molecular mechanism underlying the loss of ER, FOXO3a, and induction of HER2 in fulvestrant-resistant breast cancer. Short-term fulvestrant treatment degraded ER proteins via the ubiquitin-proteasome degradation pathway in MCF7 cells. MCF7 cells turn into highly proliferative cells (fulvestrant-resistant cells: Ful-R) after long-term fulvestrant treatment. These cells exhibit markedly suppressed estrogen and progesterone receptor levels. The phosphorylation of EGFR, HER2, and ERK was induced in Ful-R, and these phosphorylation inhibitors suppressed cell proliferation in Ful-R.

Key Molecule: Oncogenic epidermal growth factor receptor (EGFR) [1]

• Resistant Disease: Triple-negative breast cancer [ICD-11: 2C60.9]
• Resistant Drug: Fulvestrant
• Molecule Alteration: Phosphorylation; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: EGFR/HER2 signaling pathway; Regulation; N.A.
• In Vitro Model: MCF7 (Ful-R) cells; Breast; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: Western blot assay
• Mechanism Description: In this study, we investigated the molecular mechanism underlying the loss of ER, FOXO3a, and induction of HER2 in fulvestrant-resistant breast cancer. Short-term fulvestrant treatment degraded ER proteins via the ubiquitin-proteasome degradation pathway in MCF7 cells. MCF7 cells turn into highly proliferative cells (fulvestrant-resistant cells: Ful-R) after long-term fulvestrant treatment. These cells exhibit markedly suppressed estrogen and progesterone receptor levels. The phosphorylation of EGFR, HER2, and ERK was induced in Ful-R, and these phosphorylation inhibitors suppressed cell proliferation in Ful-R.

Key Molecule: Estrogen receptor (ESR1) [1]

• Resistant Disease: Triple-negative breast cancer [ICD-11: 2C60.9]
• Resistant Drug: Fulvestrant
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: EGFR/HER2 signaling pathway; Regulation; N.A.
• In Vitro Model: MCF7 (Ful-R) cells; Breast; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: qRT-PCR
• Mechanism Description: In this study, we investigated the molecular mechanism underlying the loss of ER, FOXO3a, and induction of HER2 in fulvestrant-resistant breast cancer. Short-term fulvestrant treatment degraded ER proteins via the ubiquitin-proteasome degradation pathway in MCF7 cells. MCF7 cells turn into highly proliferative cells (fulvestrant-resistant cells: Ful-R) after long-term fulvestrant treatment. These cells exhibit markedly suppressed estrogen and progesterone receptor levels. The phosphorylation of EGFR, HER2, and ERK was induced in Ful-R, and these phosphorylation inhibitors suppressed cell proliferation in Ful-R.

Key Molecule: Receptor tyrosine-protein kinase erbB-2 (ERBB2) [1]

• Resistant Disease: Triple-negative breast cancer [ICD-11: 2C60.9]
• Resistant Drug: Fulvestrant
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: EGFR/HER2 signaling pathway; Regulation; N.A.
• In Vitro Model: MCF7 (Ful-R) cells; Breast; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: Western blot assay
• Mechanism Description: In this study, we investigated the molecular mechanism underlying the loss of ER, FOXO3a, and induction of HER2 in fulvestrant-resistant breast cancer. Short-term fulvestrant treatment degraded ER proteins via the ubiquitin-proteasome degradation pathway in MCF7 cells. MCF7 cells turn into highly proliferative cells (fulvestrant-resistant cells: Ful-R) after long-term fulvestrant treatment. These cells exhibit markedly suppressed estrogen and progesterone receptor levels. The phosphorylation of EGFR, HER2, and ERK was induced in Ful-R, and these phosphorylation inhibitors suppressed cell proliferation in Ful-R.

Key Molecule: Receptor tyrosine-protein kinase erbB-2 (ERBB2) [1]

• Resistant Disease: Triple-negative breast cancer [ICD-11: 2C60.9]
• Resistant Drug: Fulvestrant
• Molecule Alteration: Phosphorylation; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: EGFR/HER2 signaling pathway; Regulation; N.A.
• In Vitro Model: MCF7 (Ful-R) cells; Breast; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: Western blot assay
• Mechanism Description: In this study, we investigated the molecular mechanism underlying the loss of ER, FOXO3a, and induction of HER2 in fulvestrant-resistant breast cancer. Short-term fulvestrant treatment degraded ER proteins via the ubiquitin-proteasome degradation pathway in MCF7 cells. MCF7 cells turn into highly proliferative cells (fulvestrant-resistant cells: Ful-R) after long-term fulvestrant treatment. These cells exhibit markedly suppressed estrogen and progesterone receptor levels. The phosphorylation of EGFR, HER2, and ERK was induced in Ful-R, and these phosphorylation inhibitors suppressed cell proliferation in Ful-R.

Palbociclib

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Metabolic Reprogramming via Altered Pathways (MRAP)

Key Molecule: Diacylglycerol kinase gamma (DGKGgamma) [2]

• Metabolic Type: Glucose metabolism
• Resistant Disease: Triple-negative breast cancer [ICD-11: 2C60.9]
• Resistant Drug: Palbociclib
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: MDA-MB-231cells; Breast; Homo sapiens (Human); CVCL_0062
• In Vitro Model: MFM-223 cells; Pleural effusion; Homo sapiens (Human); CVCL_1408
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: Cell viability assay
• Mechanism Description: This study aims to identify differentially expressed genes (DEG) associated with acquired resistance to palbociclib in ER- breast cancer cells.

References

• Ref 1: Loss of ERalpha involved-HER2 induction mediated by the FOXO3a signaling pathway in fulvestrant-resistant breast cancer. Biochem Biophys Res Commun. 2025 Jan;742:151056.
• Ref 2: Differential gene expression analysis of palbociclib-resistant TNBC via RNA-seq. Breast Cancer Res Treat. 2021 Apr;186(3):677-686.