Parathyroid Hormone-Related Peptide (PTHrP) as a New Target for Metastatic Breast Cancer: Evaluation in Preclinical Models
Technical Report,30 Sep 2015,29 Sep 2016
Research Institute of McGill University Montral, QC Canada
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The purpose of this study is to investigate the role of parathyroid hormone-related protein PTHrP in cancer stem cell-driven triple-negative breast cancer. Our goal is to confirm PTHrP as a targetable molecular driver in order to develop better therapies against this notoriously hard-to-treat family of cancers. We have now constructed animal models with mammary epithelium fluorescent labelled cells to allow tracing of cancer stem cells from the primary mammary tumor to the metastatic site. We will use these models to compare cancer stem cell behavior in PTHrP-ablated and non-ablated animals. Using CRISPr technology, we are developing pre-clinical PTHrP-ablated human triple-negative breast cancer cell lines to test the cancer-blocking efficacy of our anti-PTHrP monoclonal antibodies and identify cell markers associated with cancer progression events. We are using a large tissue bank from triple-negative breast cancer patient tumors to investigate the relationship between triple-negative breast cancer tumoral PTHrP expression levels and cancer recurrence. The goal is also to develop a method to identify patients who would benefit from a novel anti-PTHrP therapy. We have already determined that PTHrP is overexpressed in the tumor tissue of the majority of triple-negative breast cancer cases.
- Medicine and Medical Research
- Genetic Engineering and Molecular Biology