Mechanisms of metastasis and development of resistance to therapy in breast cancer. A clinical case of the effectiveness of ixabepilone in hormone-receptorpositive breast cancer with multidrug resistance

Abstract

Metastatic breast cancer occupies a leading position in the structure of mortality among women with oncological diseases worldwide. At the same time, the control of metastatic disease remains a significant problem for clinical oncology despite the improvement of early screening indicators, as well as the introduction of targeted therapy in clinical practice. An increase in the tumor stemness and the epithelial-mesenchymal transition in the primary tumor leads to the plasticity of the tumor cell. This is realized in the progression of the disease, resistance to the therapy and the appearance of distant metastases. Numerous signaling pathways, including PI3K/APK, STAT3, Wnt, Hedgehog, and Notch, play a key role in maintaining cellular plasticity in breast cancer. Understanding the cellular mechanisms of breast cancer cell plasticity with the development of multidrug resistance is a prerequisite for the development of effective therapeutic strategies against metastatic breast cancer in late-line therapy. The article presents an overview of the current understanding of the biological mechanism of the metastatic cascade and resistance to therapy. It is from the point of view of the plasticity of the tumor cell and the increase in the stemness of the tumor that the resistance to treatment is considered. The effectiveness of the representative of Ixabepilone was analyzed in the case of its use in the late-line therapy of hormone-receptor-positive breast cancer with multidrug resistance.

Keywords

• breast cancer
• metastatic cancer
• tumor stem cell
• multidrug resistance
• ixabepilone