scholarly journals VEGFR-1 (Flt1) and VEGFR-3 (Flt4) are expressed at higher levels in the tumors of breast cancer patients treated with trastuzumab.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Growth Factor ◽  
Growth Control ◽  
Growth Factor Receptor ◽  
Control Mechanisms ◽  
Breast Cancer Patients ◽  
Primary Tumors ◽  
Tumor Growth Factor ◽  
Microarray Datasets ◽  
Endothelial Growth Factor

Patients treated with trastuzumab experience a brain metastasis rate of up to 34% (1). While the mechanism of action of trastuzumab is thought to involve binding of the Fab region of trastuzumab to the extracellular portion of the human epidermal growth factor receptor 2 (HER2) (2), the transcriptional consequences of such binding events are less well understood. We mined published microarray datasets (3, 4) to understand in an unbiased fashion the genes most transcriptionally perturbed following trastuzumab treatment in patients with breast cancer. We identified transcriptome-wide differential expression of FLT1 (5, 6) and FLT4 (7-10), also known as the vascular endothelial growth factor receptors VEGFR-1 and VEGFR-3. VEGFR-1 and VEGFR-3 were expressed at higher levels in the primary tumors of patients treated with trastuzumab, raising concerns over the use of trastuzumab in a patient population already battling evasion of growth control mechanisms through tumor growth factor signals.

scholarly journals The placental growth factor (PGF) is differentially expressed in the primary tumors of breast cancer patients treated with trastuzumab.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Growth Factor ◽  
Growth Factor Receptor ◽  
Placental Growth Factor ◽  
Differentially Expressed ◽  
Expression Data ◽  
Breast Cancer Patients ◽  
Primary Tumors ◽  
Epidermal Growth ◽  
The Brain

Trastuzumab, a monoclonal antibody targeted against the human epidermal growth factor receptor 2 (HER2) is utilized for the treatment of human breast cancer (1, 2), but a complete understanding of how tumor signal transduction is modulated by trastuzumab treatment is lacking. By mining published and public microarray and gene expression data (3, 4) from the primary tumors of patients treated with trastuzumab, we found that the placental growth factor, encoded by PGF was among the genes most differentially expressed in the primary tumors of patients treated with trastuzumab, and expressed at lower levels in the tumors of patients treated with trastuzumab. Thus, the use of trastuzumab in patients with breast cancer is associated with increased expression of a growth factor that is chemotactic, angiogenic (5) and important for growth of blood vessels in the brain (6).

scholarly journals FGF10 is differentially expressed in the tumors of breast cancer patients treated with trastuzumab.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Growth Factor ◽  
Cancer Patients ◽  
Messenger Rna ◽  
Growth Factor Receptor ◽  
Metastatic Breast ◽  
The United States ◽  
Differentially Expressed ◽  
Breast Cancer Patients ◽  
Primary Tumors

Trastuzumab (Herceptin) is a monoclonal antibody targeting the extracellular domain of the human epidermal growth factor receptor 2 (HER2) (1) utilized for the treatment of adjuvant and metastatic breast cancer (2) in the United States and worldwide. We mined published microarray and gene expression data (3, 4) to discover in an unbiased manner the most significant transcriptional changes associated with trastuzumab treatment. We identified FGF10 among the genes most differentially expressed in the primary tumors of patients with breast cancer treated with trastuzumab. The primary tumors of breast cancer patients treated with trastuzumab expressed higher levels of FGF10 messenger RNA than did patients not treated with trastuzumab, and a single administration of trastuzumab was sufficient to result in differential expression of FGF10 in primary tumors of the breast, demonstrating increased expression of a growth factor which provides signals to support development of the limbs and for the differentiation of radial glial cells from neuronal progenitor cells (5-7) as a direct transcriptional consequence of treatment with trastuzumab.

scholarly journals IGF2 is differentially expressed in the tumors of breast cancer patients treated with trastuzumab.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Growth Factor ◽  
Cancer Patients ◽  
Messenger Rna ◽  
Growth Factor Receptor ◽  
Metastatic Breast ◽  
The United States ◽  
Differentially Expressed ◽  
Breast Cancer Patients ◽  
Primary Tumors

Trastuzumab (Herceptin) is a monoclonal antibody targeting the extracellular domain of the human epidermal growth factor receptor 2 (HER2) (1) utilized for the treatment of adjuvant and metastatic breast cancer (2) in the United States and worldwide. We mined published microarray and gene expression data (3, 4) to discover in an unbiased manner the most significant transcriptional changes associated with trastuzumab treatment. We identified the growth factor IGF2 as among the genes most differentially expressed in the primary tumors of patients with breast cancer treated with trastuzumab. The primary tumors of breast cancer patients treated with trastuzumab expressed significantly higher levels of IGF2 messenger RNA than did patients not treated with trastuzumab, and a single administration of trastuzumab was sufficient to result in differential expression of IGF2 in primary tumors of the breast, demonstrating increased expression of a growth factor encoded at a paternally imprinted locus (5) as a direct transcriptional result of treatment with trastuzumab.

scholarly journals Transcriptional induction of the nerve growth factor receptor in the primary tumors of breast cancer patients treated with trastuzumab.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Nerve Growth Factor ◽  
Growth Factor ◽  
Cancer Patients ◽  
Growth Factor Receptor ◽  
Breast Cancer Patients ◽  
Primary Tumors ◽  
Nerve Growth ◽  
Trastuzumab Treatment ◽  
Transcriptional Induction

The incidence of central nervous system metastases in breast cancer patients treated with the human epidermal growth factor receptor 2 (HER2) monoclonal antibody trastuzumab has been reported at 34% (1). To understand the most significant transcriptional changes associated with trastuzumab treatment in patients with breast cancer, we mined published microarray and multiplexed gene expression data (2, 3), comparing the primary tumors of patients treated with trastuzumab or not. We identified significant differential expression and transcriptional induction of the nerve growth factor receptor, NGFR, in the primary tumors and tumor cells of breast cancer patients treated with trastuzumab. We suggest up-regulation of a receptor for a neurotrophic growth factor is a highly undesirable consequence of trastuzumab treatment in a population prone to develop metastases to the brain.

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