Transcriptomic analysis of mammary tumor biospy from MMTV-ErbB2 transgenic mice [Doxorubicin]
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ABSTRACT: The tyrosine kinase ErbB2 positive breast tumors have more aggressive tumor growth, poorer clinical outcome, and more resistance to radiotherapy, chemotherapy and hormone therapy. To identify the biomarkers for predicting the responses to chemotherapy, we treated genetically diverse F1 backcross (F1Bx) mice between C57BL/6J and FVB/N MMTV-Erbb2 transgenic mice with mammary tumor by doxorubicin. Biopsies were taken in sterile conditions and processed for RNA and histological analysis before treatment. This will help us to have a better understanding of the heterogeneous response to chemotherapy and permit us to design better and more individualized (personalized) treatment strategies for human ErbB2 positive breast cancer.
Project description:The tyrosine kinase ErbB2 positive breast tumors have more aggressive tumor growth, poorer clinical outcome, and more resistance to radiotherapy, chemotherapy and hormone therapy. To identify the biomarkers for predicting the responses to chemotherapy, we treated genetically diverse F1 backcross (F1Bx) mice between C57BL/6J and FVB/N MMTV-Erbb2 transgenic mice with mammary tumor by docetaxel. Biopsies were taken in sterile conditions and processed for RNA and histological analysis before treatment. This will help us to have a better understanding of the heterogeneous response to chemotherapy and permit us to design better and more individualized (personalized) treatment strategies for human ErbB2 positive breast cancer.
Project description:The tyrosine kinase ErbB2 positive breast tumors have more aggressive tumor growth, poorer clinical outcome, and more resistance to radiotherapy, chemotherapy and hormone therapy. A humanized anti-ErbB2 monoclonal antibody Herceptin and a small molecules inhibitor Lapatinib were developed and approved by FDA to treat patients with ErbB2 amplification and overexpression. Unfortunately, most ErbB2+ breast cancers do not respond to Herceptin and Lapatinib, and the majority of responders become resistant within 12 months of initial therapy (defined as secondary drug resistance). Such differences in response to Lapatinib treatment is contributed by substantial heterogeneity within ErbB2+ breast cancers. To address this possibility, we carried out transcriptomic analysis of mammary tumors from genetically diverse MMTV-ErbB2 mice. This will help us to have a better understanding of the heterogeneous response to ErbB2 targeted therapy and permit us to design better and more individualized (personalized) treatment strategies for human ErbB2 positive breast cancer. 214 MMTV-ErbB2 mammary tumors and 8 normal mammary glands were analyzed by Affymetrix microarrays.
Project description:The tyrosine kinase ErbB2 positive breast tumors have more aggressive tumor growth, poorer clinical outcome, and more resistance to radiotherapy, chemotherapy and hormone therapy. A humanized anti-ErbB2 monoclonal antibody Herceptin and a small molecules inhibitor Lapatinib were developed and approved by FDA to treat patients with ErbB2 amplification and overexpression. Unfortunately, most ErbB2+ breast cancers do not respond to Herceptin and Lapatinib, and the majority of responders become resistant within 12 months of initial therapy (defined as secondary drug resistance). Such differences in response to Lapatinib treatment is contributed by substantial heterogeneity within ErbB2+ breast cancers. To address this possibility, we carried out transcriptomic analysis of mammary tumors from genetically diverse MMTV-ErbB2 mice. This will help us to have a better understanding of the heterogeneous response to ErbB2 targeted therapy and permit us to design better and more individualized (personalized) treatment strategies for human ErbB2 positive breast cancer.
Project description:This study provides site-specific profiles of asparagine-linked and serine/threonine-linked glycosylations on ErbB2, a therapeutic target RTK for ErbB2-positive cancer, through structural analysis of recombinant ErbB2 extracellular region and endogenous ErbB2 from ErbB2-positive breast cancer cells.
Project description:This study provides site-specific profiles of asparagine-linked and serine/threonine-linked glycosylations on ErbB2, a therapeutic target RTK for ErbB2-positive cancer, through structural analysis of recombinant ErbB2 extracellular region and endogenous ErbB2 from ErbB2-positive breast cancer cells. Furthermore, comparison of the N-glycosylated structures of the extracellular regions of ErbB2 and its homologue, the epidermal growth factor receptor (EGFR), showed differences in the distribution and density of N-glycans on both molecules, providing new insights into the different activation mechanisms of ErbB2 and EGFR from a glycan perspective.
Project description:EGFR-inhibition is required for targeted therapies of ERBB2-positive/EGFR high breast cancer. Approximately 30% of human ERBB2-positive breast tumors also express EGFR.
Project description:EGFR-inhibition is required for targeted therapies of ERBB2-positive/EGFR high breast cancer. Approximately 30% of human ERBB2-positive breast tumors also express EGFR.
Project description:EGFR-inhibition is required for targeted therapies of ERBB2-positive/EGFR high breast cancer. Approximately 30% of human ERBB2-positive breast tumors also express EGFR.
Project description:EGFR-inhibition is required for targeted therapies of EGFR high/ERBB2 positive breast cancer. Approximately 30% of human ERBB2 positive breast tumors also express EGFR.
Project description:EGFR-inhibition is required for targeted therapies of ERBB2-positive/EGFR high breast cancer. Approximately 30% of human ERBB2-positive breast tumors also express EGFR.