Raf kinases and receptor tyrosine kinases (RAF/RTK)

Raf kinases and receptor tyrosine kinases (RTKs) are integral components of the Ras-Raf-MEK-ERK signaling pathway, a fundamental axis regulating cell growth, survival, and differentiation (Wellbrock et al., 2004). RTKs are cell-surface receptors that trigger intracellular signaling upon activation by growth factors, while Raf kinases (A-Raf, B-Raf, and C-Raf) serve as critical serine/threonine-specific nodes that relay these signals to the nucleus (Lemmon & Schlessinger, 2010). Aberrant activation of this axis, frequently driven by mutations in BRAF or overexpression of RTKs like VEGFR and EGFR, is a primary driver in many human cancers, including melanoma and renal cell carcinoma (Davies et al., 2002). Multi-kinase inhibitors such as sorafenib and regorafenib have been developed to target both the Raf family and various RTKs, providing a dual mechanism that inhibits both tumor cell proliferation and tumor-associated angiogenesis (Wilhelm et al., 2004). Understanding the interplay between these kinases is essential for managing drug resistance, which often arises through compensatory signaling or feedback loops within this network (Nature Reviews Cancer, 2014). This target entry is classified as incorrect because it combines two distinct protein families into a single entity rather than specifying a single molecular target.

Other names

RAF/MEK/ERK pathway componentsRTK/RAS/RAF signaling moduleMAPK pathway kinasesReceptor tyrosine kinase/Raf signaling axis

Inhibition of the ATP-binding site within the catalytic kinase domain of both receptor tyrosine kinases (RTKs) and Raf serine/threonine kinases, thereby preventing the phosphorylation of downstream substrates (such as MEK) and disrupting the MAPK/ERK signaling cascade (Wilhelm et al., 2004; NIH/NCI).