Paclitaxel in breast cancer – drug resistance and strategies to counteract it

Abstract

Despite significant progress in the last few decades in breast cancer biology and the use of different therapeutic strategies, this cancer remains a serious clinical problem. Paclitaxel (PTX) is used to treat breast cancer both as a monotherapy and in combination with other anticancer drugs depending on the severity of the cancer, the presence of metastases and previous therapeutic management. It is characterized by high effectiveness both in early breast cancer and in metastatic breast cancer. Primary or acquired drug resistance of tumour cells to taxanes is a significant clinical problem in the treatment of various histological types of breast cancer. The main problem of resistance of tumour cells is the complexity and multifactorial nature of this phenomenon, which is conditioned by numerous different mechanisms that interact with each other. Among the known mechanisms of breast cancer cells resistance to PTX, the most important are the active removal of the drug from the cell related to the increased activity of ABC family membrane transporters, enhanced drug detoxification by cytochrome P450, CYP3A4/5 and CYP2C8 enzymes, changes within the molecular targets of PTX, microtubule and disorders of microtubule associated protein (MAPs) or apoptosis. This paper presents the latest reports on the mechanisms of drug resistance of breast cancer cells to PTX, pointing to modern strategies to counteract this adverse phenomenon.