Raf kinases and associated receptor tyrosine kinases (Raf/RTK)

Raf kinases and associated receptor tyrosine kinases represent a multi-protein target profile central to oncogenic signaling and tumor angiogenesis. The Raf family, including A-Raf, B-Raf, and C-Raf (Raf-1), functions as serine/threonine kinases within the MAPK/ERK pathway to regulate cell proliferation and survival (UniProt P15056, P04049). Associated receptor tyrosine kinases (RTKs), such as Vascular Endothelial Growth Factor Receptors (VEGFR-1, -2, -3) and Platelet-Derived Growth Factor Receptor-beta (PDGFR-beta), are critical for mediating angiogenesis and the recruitment of perivascular cells (PubMed 14758358). In many malignancies, including hepatocellular carcinoma and renal cell carcinoma, these pathways are pathologically activated, driving tumor growth and vascularization (StatPearls NBK534868). Drugs targeting this collective group, known as multi-kinase inhibitors, aim to simultaneously disrupt both tumor cell signaling and the supporting vascular microenvironment. For instance, sorafenib and regorafenib inhibit these kinases to induce apoptosis and reduce tumor blood flow (FDA Label). However, the broad inhibition of these diverse kinases often results in characteristic adverse effects such as hand-foot skin reaction and hypertension (PubMed 21571866).

Other names

MAPK pathway and angiogenic RTKsRaf/VEGFR/PDGFR complexMulti-kinase inhibitor targetsRaf/MEK/ERK and RTK signaling nodes

Simultaneous inhibition of the Raf/MEK/ERK signaling pathway (via Raf kinases) and the inhibition of receptor tyrosine kinases (RTKs) involved in angiogenesis and lymphangiogenesis, such as VEGFR and PDGFR.