Receptor tyrosine kinase profile (TAM, VEGFR2, KIT, MET) (TAM/VEGFR2/KIT/MET)

The target profile comprising TYRO3, AXL, MERTK (TAM receptors), VEGFR2, KIT, and MET represents a complex of receptor tyrosine kinases (RTKs) that drive oncogenesis, angiogenesis, and immune evasion [1][2]. VEGFR2 is the primary driver of vascular endothelial growth and permeability, while MET and the TAM family are implicated in promoting tumor cell motility, invasion, and resistance to apoptosis [3][4]. KIT is essential for the maintenance of hematopoietic stem cells and is a known driver in gastrointestinal stromal tumors [5]. This specific multi-target signature is the primary focus of multi-kinase inhibitors like cabozantinib, which aim to disrupt the tumor microenvironment and inhibit tumor cell intrinsic signaling simultaneously [6]. By targeting these diverse pathways, therapeutic intervention seeks to prevent the compensatory signaling that typically leads to resistance against more selective inhibitors [7]. [1] UniProt (P15151, P30530, Q06418, P35968, P10721, P08581). [2] NIH/NCI Drug Dictionary (Cabozantinib). [3] Graham, D. K., et al. (2014). "The TAM family: phosphatidylserine-sensing receptor tyrosine kinases gone awry in cancer." Nature Reviews Cancer. [4] Gherardi, E., et al. (2012). "Targeting MET in cancer: rationale and progress." Nature Reviews Cancer. [5] Lennartsson, J., & Rönnstrand, L. (2012). "Stem cell factor receptor/c-Kit: from basic science to clinical implications." Physiological Reviews. [6] Yakes, F. M., et al. (2011). "Cabozantinib (XL184), a novel MET and VEGFR2 inhibitor, simultaneously suppresses metastasis, angiogenesis, and tumor growth." Molecular Cancer Therapeutics. [7] Zhou, L., et al. (2020). "TAM receptor signaling in cancer." Signal Transduction and Targeted Therapy.

Other names

TAM receptors (TYRO3, AXL, MERTK)Vascular endothelial growth factor receptor 2 (VEGFR2/KDR)Mast/stem cell growth factor receptor Kit (c-Kit/CD117)Hepatocyte growth factor receptor (HGFR/MET)

Inhibition of the intracellular tyrosine kinase domains of TYRO3, AXL, MERTK, VEGFR2, KIT, and MET, thereby blocking downstream signaling pathways such as PI3K/AKT, MAPK/ERK, and STAT3 to suppress tumor growth, metastasis, and angiogenesis.