Figure 2.

Mechanisms of action of monoclonal antibodies vs. small molecule tyrosine kinase inhibitors (TKIs). Ligand (L) binding to RTKs leads to receptor dimerization, cross phosphorylation (red lines and P), and activation of the intracellular tyrosine kinase domain (red boxes). Substrates are then phosphorylated, leading to cellular responses. Monoclonal antibodies (mAbs, Top) interfere with ligand binding to receptor and/or receptor dimerization and cross-phosphorylation, blocking activation of the RTKs.¹⁷ TKIs (Bottom) do not prevent ligand binding or dimerization, but by preventing ATP from binding to the kinase domain, they block cross-phosphorylation of receptors and phosphorylation of substrates.