Iesato A, Li S, Roti G, et al. - Tyrosine-kinases (TK, eg PDGFR-β) are abundantly expressed by pericyte populations which affect therapeutic response. Lenvatinib, a clinically available TK inhibitor (TKI), targets PDGFR-β. Patients with greater disease burden and metastasis had a shorter duration of therapeutic response. In this study, gene signature of pericyte abundance was developed that may aid in assessing tumor aggressiveness, and determining both the response of thyroid-derived pericytes to lenvatinib and their synergies with thyroid carcinoma-derived cells. In BRAF V600E-PTC with hTERT mutations and copy number alterations, significantly higher pericyte abundance was noted compared with NT or BRAF WT-PTC samples. Upregulated pathways important for tumor survival, immunomodulation, RNA transcription, cell cycle regulation, cholesterol metabolism were also identified. PDGF-BB, which activates phospho(p)-PDGFR-β, pERK1/2 and pAKT, led to significant increase in pericyte growth. Lenvatinib was identified as a strong inhibitor of pericyte viability which involves down-regulation MAPK, pAKT and p-p70S6-kinase downstream PDGFR-β. As a result of pericyte targeting via PDGFR-β, lenvatinib led to significant induction of higher BRAF WT/V600E-PTC cell death when co-cultured with pericytes.