New chemotherapy resistance mechanism in the inflammatory breast cancer triple negative -
Researchers at Roswell Park Cancer Institute (RPCI) identified a cancer cell mechanism within which lead to resistance to chemotherapy in the inflammatory breast cancer. These preclinical findings, published online ahead of print in the International Journal of Oncology, provide evidence of a potential therapeutic approach that will restore sensitivity to chemotherapy and improve tumor treatment of inflammatory breast cancer.
"This study provides the basis for future research in patients with breast cancer and offers hope for targeted therapy for patients with aggressive triple negative breast cancer inflammatory" said lead researcher Mateusz Opyrchal, MD, Ph.D., assistant professor of oncology at RPCI.
Inflammatory breast cancer is the most aggressive type of advanced breast cancer and is characterized by rapid development, resistance to chemotherapy, early metastasis and poor prognosis. of inflammatory breast cancer cells have a triple negative breast cancer phenotype that does not have the necessary receptors to promote tumor growth. Therefore, the usual treatments such as endocrine therapy and molecular targeting the HER-2 receptor are not effective in this subtype of breast cancer. No targeted therapy approved for breast cancer tumors triple negative non-inflammatory and inflammatory, and the standard treatment for these tumors is a combination of conventional cytotoxic chemotherapeutic agents.
In the laboratory, Dr. Opyrchal and colleagues used breast cancer cell lines to determine the extent to which chromosomal instability and resistance to chemotherapy - the characteristics of inflammatory breast cancer - are related to CD44 + / CD24- / low phenotype rod. They found that CD44 + / CD24- / Bas cancer stem cell (TLC) were resistant to conventional chemotherapy, but were sensitive to SU9516, a specific cyclin-dependent kinase 2 (Cdk2) inhibitor. The researchers concluded from these results that the aberrant activation of cyclin E / Cdk2 oncogenic signaling is essential for the maintenance and expansion of CD44 + / CD24- / Down in inflammatory breast cancer subpopulation. Therefore, a new therapeutic approach in inflammatory breast cancer may involve a combination of conventional chemotherapy with small molecule inhibitors of the kinase Cdk2 cell cycle.
"Cdk2 cell cycle kinase appears to play a role in cancer cell's ability to be more aggressive and resistant to standard chemotherapy," said Dr. Opyrchal. "The blocking of its function has resulted in improving the ability of chemotherapy drugs to kill cancer cells. Cancer stem cells should be identified and processed in a manner different from that of the bulk tumor."
Dr. Opyrchal note that these results should be confirmed before human trials can be planned. His lab continues to work on identifying cancer stem cells and the signaling pathways that play a role in growth, metastatic potential and resistance to standard treatments.
The study "Inhibition of Cdk2 kinase activity selectively target CD44 + / CD24 -. / Down subpopulation and stem cells restores chemosensitivity SUM149PT triple-negative breast cancer, "was supported in part by the National Cancer Institute (NCI) grants R01CA072836 and P50CA116201
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