Targeted therapies in breast cancer: New challenges to fight against resistance

Figure 1 A schematic diagram of the most common resistance mechanisms to targeted therapies. (1) Alteration of the drug target (Treat.): This type of resistance involves mutations as well as amplifications of drug targets such as kinases; (2) Upstream and downstream pathway effect through the activation of receptor tyrosine kinase (RTK) (a) and/or the mutation/amplification of upstream (b) or downstream (c) components; (3) Bypass mechanisms occur as a result of a second receptor tyrosine kinase activation (a), through a mutation of a parallel kinase (b) or modulation of mRNA binding proteins (c). These alternative mechanisms of resistance especially through kinases activation result in the modification of gene expression via the phosphorylation or transcription factors (TF).