mTOR inhibition, a potential novel approach for bronchial carcinoids

Although targeted therapy, including inhibitors of mammalian target of rapamycin (mTOR) and vascular endothelial growth factor, being developed for carcinoids arised from the gastrointestinal tract, treatment for locally advanced or metastatic bronchial carcinoids (BCs) remains lacking. Traditional cytotoxic chemotherapy offers essentially minimal benefit to this largely under-characterized tumor. In the September issue of Endocrine-Related Cancer, Zatelli et al. reported an anti-proliferative effect of mTOR inhibitor, everolimus, in cultured primary BC tumor cells by attenuation of IGF signaling pathway. This effect is more significant in aggressive tumors that carry higher levels of mTOR, and is consistent with the therapeutic benefit of everolimus for patients with BC observed in our phase II and III clinical trials. Although adding somatostatin analog to mTOR inhibitor did not provide a synergistic anti-tumor effect, development of rational combinations is highly warranted to further improve the outcome for patients with neuroendocrine tumors.