Fig. 8: Schematic diagram of FGF-2-FGFR1-ERK-MYC axis mediates AAD resistance and metastasis in NPC.
From: Lenvatinib for effectively treating antiangiogenic drug-resistant nasopharyngeal carcinoma
NPC cancer cells often produce FGF-2, and FGF-2 impedes the AAD-mediated anti-EC effect in the TME. In FGF-2 positive tumors, the FGFR1-ERK-MYC axis is upregulated in ECs and compensates for VEGF-VEGFR2-MYC signaling. MYC further drives downstream angiogenic genes, hence keep the angiogenesis in the TME. Angiogenic tumor vessels further facilitate tumor cell intravasation and pulmonary metastasis. In such FGF-2 high TME, inhibition of VEGF-VEGFR2 signaling alone does not effectively inhibit angiogenesis. Lenvatinib, an FDA-approved multi-kinase inhibitor targeting both VEGFR2 and FGFR1, exhibits robust antiangiogenic and anti-tumor effects in NPC or possibly FGF-2-rich tumors.
