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Breast cancer anti-estrogen resistance 4 (BCAR4)
- Target
- BCAR4
- Molecular classification
- Long non-coding RNA (lncRNA), Protein-coding gene or peptide (controversial; some sources report translated product), Other (maternal-effect gene in oocytes)
01
Overview
Breast cancer anti-estrogen resistance 4 (BCAR4) is a gene most widely characterized as a long non-coding RNA, though some evidence has supported low-level protein-coding potential. BCAR4 drives cell proliferation, migration, and endocrine resistance, particularly in breast cancer cells, through pathways independent of estrogen receptor signaling (such as ERBB2/3 and non-canonical Hedgehog/GLI2 or Wnt/β-catenin). High expression of BCAR4 is associated with poor clinical outcomes: reduced benefit from tamoxifen, rapid tumor growth, and metastasis in breast cancer, and similar oncogenic effects in colon and lung cancers. The gene exhibits restricted expression in human tissues, being highly expressed in placenta and oocyte, and mostly absent elsewhere except in cancer. Lapatinib, a dual EGFR/ERBB2 inhibitor, can reduce proliferation in BCAR4-driven cancer models. BCAR4 is being explored as a prognostic biomarker and potential therapeutic target in cancers characterized by endocrine resistance and aggressive growth.
- Other names
- Breast cancer anti-estrogen resistance 4 (non-protein coding)BCAR4breast cancer antiestrogen resistance 4 protein
02
Mechanism of action
Lapatinib: inhibits ERBB2/EGFR signaling promoted by BCAR4; Tamoxifen: anti-estrogenic, but resistance is caused by BCAR4 expression
03
Biological functions
Cell proliferationAnti-estrogen resistanceSignal transduction (Wnt/β-catenin pathway, ERBB2/3 activation, Hedgehog/GLI2 pathway)Cell migrationTumorigenesis
04
Disease associations
Cancer (particularly breast cancer, colon cancer, lung cancer)Endocrine resistance in cancer
05
Safety considerations
Selectivity: BCAR4 is highly expressed in placenta and oocyte but rare in other normal tissues, indicating potentially limited off-target toxicity; more data neededPotential for resistance to targeted therapy as observed in other oncogenes
06
Interacting drugs
Lapatinib
1 more in the full profile.
07
Biomarkers
BCAR4 mRNA expression levels (predict resistance to antiestrogens, worse survival, efficacy of neoadjuvant chemotherapy in locally advanced breast cancer)
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