Multiple endogenous growth factor receptors and prosurvival pathways

The term 'Multiple endogenous growth factor receptors and prosurvival pathways' refers to a broad therapeutic strategy of simultaneously inhibiting various receptor tyrosine kinases (RTKs) and their downstream intracellular signaling cascades. Common growth factor receptors involved include the Vascular Endothelial Growth Factor Receptor (VEGFR), Platelet-Derived Growth Factor Receptor (PDGFR), and Fibroblast Growth Factor Receptor (FGFR) (Source: NIH, PMC1571287). Pro-survival pathways typically include the PI3K/AKT/mTOR and RAF/MEK/ERK pathways, which are frequently dysregulated in various malignancies to promote cell growth and evade apoptosis (Source: PubMed, 17011679). By targeting multiple nodes within these networks, multi-kinase inhibitors can overcome compensatory signaling mechanisms that often lead to drug resistance. This approach is a hallmark of several approved oncology drugs, such as sorafenib and sunitinib, which are used to treat advanced renal and hepatocellular carcinomas (Source: StatPearls, NBK563262). These drugs bind to the ATP-binding sites of the kinases, preventing phosphorylation and subsequent signal transduction. While effective, the broad inhibition of these essential pathways often leads to significant systemic side effects like hypertension and skin toxicity.

Other names

Multikinase targetsRTK and pro-survival signaling networkGrowth factor signaling pathways

Simultaneous inhibition of multiple cell surface receptor tyrosine kinases and downstream intracellular signaling components to block proliferative and anti-apoptotic signals.