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