Biopsy-driven study to identify biomarkers of drug resistance in patients with triple-negative breast cancer
| Autor: | Manuela Pelmus, Mark Basik, Elizabeth A. Marcus, Gerald Batist, Josiane P. Lafleur, Carole Seguin, Catalin Mihalcioiu, Zuanel Diaz, André Robidoux, Ewa Przybytkowski, Josee-Anne Roy, Adriana Aguilar-Mahecha, Christine Desbiens, Elaheh Ahmadzadeh |
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| Rok vydání: | 2012 |
| Předmět: | |
| Zdroj: | Journal of Clinical Oncology. 30:87-87 |
| ISSN: | 1527-7755 0732-183X |
| DOI: | 10.1200/jco.2012.30.30_suppl.87 |
| Popis: | 87 Background: Resistance to chemotherapy is the underlying cause of death in most patients dying of breast cancer. Patients with early stages of breast cancer whose tumor is or becomes resistant to chemotherapy have a poor prognosis, while women with advanced breast cancer live as long as their tumors respond to chemotherapy. Because of the great difficulty of obtaining clinical samples from drug resistant tumors in patients, there is scant information about molecular factors from actual drug resistant tumors. This project aims to systematically profile resistant triple negative breast cancers (TNBCs) in order to discover molecular “resistance” genes/proteins as a first step to develop strategies to overcome drug resistance. Methods: Paired biopsies are collected from TNBC patients (NCT01276899). Four needle core biopsies are collected before the initiation of treatment and 2 weeks before surgery or at the time of progression in the neoadjuvant and metastatic settings respectively. Paired biopsies will undergo Next Gen Sequencing, flow sorted aCGH analysis, gene expression and miRNA profiling as well as phosphoproteomic profiling using reverse phase protein arrays. Results: We have currently enrolled 28 patients in the neoadjuvant setting and 3 metastatic patients. We have standardized the methods of collection and processing of tissue and blood specimens to ensure their molecular integrity and compatibility with different genomic and proteomic molecular platforms. Analysis of tumor cellularity has been incorporated into our quality control and we have optimized the extraction of nucleic acids to obtain high yields and optimal quality. In parallel, we have generated acquired resistance to paclitaxel in a panel of TNBC cell lines. These cell lines will also undergo genomic profiling and exome sequencing to identify molecular markers of resistance that will be correlated with the markers found in patient samples. Conclusions: This project will allow us to identify the molecular factors responsible for drug resistance in TNBCs and enable the elaboration of strategies to overcome resistance. |
| Databáze: | OpenAIRE |
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