This article reviews current knowledge on epothilones, a new class of cytotoxic agents that have recently shown activity in MBC that is resistant to multiple prior therapies.
Mechanisms of Resistance to Anthracyclines and Taxanes in Breast Cancer
Resistance to chemotherapy manifests as tumour insensitivity to initial treatment (known as intrinsic or primary resistance) or occurs after an initial response to therapy (acquired resistance). Acquired resistancemay develop during chemotherapy due to the emergence of a subpopulation of intrinsically resistant cells. The main cellular mechanisms involved in the development of tumour resistance to treatment include alterations in drug efflux, microtubule alterations, inadequate induction of apoptotic signalling and altered drug metabolism. Of these, the most recognised are alterations of drug efflux mechanisms involving members of the adenosine–triphosphate (ATP)-binding cassette (ABC) membrane transporter family, particularly P-glycoprotein (P-gp) encoded by the MDR1 gene, multidrug-resistant protein 1 (MRP1) and breast cancer-resistance protein (BRCP) encoded by the MXR gene.6,7