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VEGFR1, VEGFR2, VEGFR3, PDGFRα, PDGFRβ, KIT, RET, RAF (VEGFRs, PDGFRs, KIT, RET, RAF)
- Target
- VEGFRs, PDGFRs, KIT, RET, RAF
- Molecular classification
- Receptor tyrosine kinase, Serine/threonine protein kinase
01
Overview
These targets are receptor tyrosine kinases (VEGFR1/2/3, PDGFRα/β, KIT, RET) and serine/threonine kinases (RAF) crucial for angiogenesis, cell proliferation, survival, and migration in both normal physiology and cancer. They mediate intracellular signaling for endothelial and tumor cells in response to ligand binding, and are often dysregulated or mutated in oncogenesis. Multikinase inhibitors targeting these molecules are approved for diverse cancer types, exploiting their collective role in tumor vascularization, growth, and metastasis.
- Other names
- FLT1KDRFLK1FLT4PDGFRAPDGFRBc-KITCD117RET proto-oncogeneBRAFRAF-1/CRAF
02
Mechanism of action
Inhibition of tyrosine kinase enzymatic activity, blocking signal transduction required for angiogenesis, tumor cell proliferation, and survival. Disruption of downstream pathways: MAPK/ERK, PI3K/AKT, PLCγ, RAS/RAF/MEK/ERK.
03
Biological functions
Signal transductionAngiogenesisCell proliferationCell migrationSurvival/apoptosisDifferentiationTumor progression/metastasis
04
Disease associations
CancerInflammationCardiovascular diseaseNeurodegenerative diseaseOther proliferative disorders
05
Safety considerations
HypertensionProteinuria and renal toxicityHand-foot skin reactionsGastrointestinal toxicities (diarrhea, mucositis)MyelosuppressionCardiac toxicity (QT prolongation, heart failure)Wound healing complicationsOff-target toxicities due to broad RTK inhibition
06
Interacting drugs
Sunitinib
7 more in the full profile.
07
Biomarkers
Mutations in BRAF (e.6., V600E/K) for RAF inhibitorsKIT mutations in gastrointestinal stromal tumors (GIST)RET fusions/mutations in thyroid and lung cancersVEGFR expression in angiogenic tumorsCirculating endothelial cells/progenitors (CEP, CEC) for VEGFR pathway efficacy monitoring (investigational)PDGFR rearrangements/mutations
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