Suppression of mTOR pathway in solid tumors: lessons learned from clinical experience in renal cell carcinoma and neuroendocrine tumors and new perspectives

Abstract

The PI3K-AKT-mTOR pathway plays role in the regulation of many cellular processes. Hyperactivation of mTOR signaling has been implicated in human carcinogenesis, representing an attractive target for cancer therapy. Among other cancer subtypes, renal cell carcinoma (RCC) and neuroendocrine tumors are relevant settings in which the deregulation of mTOR pathway is of crucial importance. Different mTOR-inhibitory agents have been developed in recent years. Temsirolimus is approved for advanced RCC; everolimus is registered for the treatment of advanced RCC, pancreatic neuroendocrine tumors and postmenopausal, hormone receptor-positive/HER2-negative, advanced breast cancer. This review is focused on the description of the clinical experience with mTOR-inhibitor agents for the treatment of advanced RCC and neuroendocrine tumors, followed by an excursus on the landscape of the ongoing research in this field.

Keywords: everolimus; mTOR inhibitors; mTOR pathway; neuroendocrine neoplasm; renal cell carcinoma; temsirolimus.