FASTING ENHANCES TKI EFFICACY ON THYROID CANCER CELLS

Tyrosine kinase inhibitors (TKIs) have emerged as a novel cancer therapy for patients with poorly differentiated, anaplastic or medullary carcinomas unresponsive to conventional treatments. The association between fasting mimicking diets and TKIs has been explored with encouraging results showing a better response with less side effects due to TKI toxicity. Here we report the role of fasting in reducing cell survival and in potentiating the anticancer activity of TKIs (Lenvatinib, Sorafenib, Vandetanib and Cabozatinib) in cultured medullary, follicular, papillary and anaplastic thyroid cancer cells. In particular, fast mimicking diet reduced cell growth in all cell types but potentiated the anticancer activity of TKIs only in follicular, medullary and TPC1 thyroid cells. TKIs significantly reduced ERK1-2 activation after 1 h in all cell types. Prolonged exposure to TKIs resulted in an improvement of ERK1-2 phosphorylation which was inhibited in the presence of starvation. We demonstrated thyroid cancer cell susceptibility to fasting and validated its role in potentiating anticancer activity of TKIs by strengthening ERK1/2 signalling inhibition.