Modulating drug resistance in metastatic breast cancer

Taxanes are widely used for the treatment of metastatic breast cancer (MBC). Many patients, however, exhibit intrinsic drug resistance or develop it following exposure to commonly used chemotherapeutics. Consequently, their treatment options are limited, and the prognosis is often poor. Resistance can develop to a single drug or to several structurally and functionally distinct agents, a phenomenon known as multidrug resistance (MDR). Drug resistance in general and the MDR phenotype in particular represent major challenges to treatment of advanced disease, because they are frequently the cause of disease progression in patients with breast cancer. The lack of effective treatment options for drug-resistant MBC highlights the unmet need for agents that can effectively treat resistant disease. This article addresses the key mechanisms underlying resistance to chemotherapy in breast cancer, which provides a basis for development of novel compounds that can treat drug-resistant disease. Novel agents that are proving to be effective in the treatment of drug-resistant MBC, such as nab-paclitaxel, ixabepilone, and modulators of apoptosis are discussed.