Figure 1.

Current strategies to overcome multidrug resistance. In addition to the well-known ABC transporters, many drug resistance mechanisms of CSCs have been identified, including ALDHs, EMT, epigenetic changes, tumor microenvironment, and stemness-related signaling pathways. The drugs that inhibit each pathway are described: (i) ABC transporter inhibitors and non-substrates; (ii) ALDH inhibitors; (iii) AMPK activators; (iv) BET inhibitors, HDAC inhibitors, and KDM1 inhibitors; (v) VEGF inhibitors, RTK inhibitors, and vascular disrupting agents; (VI) Notch inhibitors, Smo inhibitors, and Wnt/β-catenin inhibitors. ABC, ATP binding cassette; ALDHs, aldehyde dehydrogenases; AMPK, AMP-activated kinase; BET, bromodomain and extra-terminal; CSCs, cancer stem cells; EMT, epithelial to mesenchymal transition; HDAC, histone deacetylase; KDM1, lysine-specific demethylase 1; MDR, multidrug resistance; RTK, receptor tyrosine kinase; VEGF, vascular endothelial growth factor.