Rationale for combining mTOR with other targeted agents in the treatment of neuroendocrine tumors
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Introduction: Advanced neuroendocrine tumors (NETs) are aggressive and incurable with standard treatment. Many cellular targets are being evaluated in this patient population, including mammalian target of rapamycin (mTOR), a kinase that is the central regulator of several signaling pathways related to cell growth, angiogenesis, and bioenergetics. Because mTOR serves as a neoplastic switch activated by many cancer-related mutations, mTOR inhibition may have broad efficacy across tumor types, including NETs. Somatostatin analogs (SSAs) have long been used to treat carcinoid symptoms in NET patients. The SSA octreotide long-acting release (LAR) demonstrated significant antitumor effects against advanced midgut NETs in the phase III PROMID study.
Aim(s): Targeting of multiple pathways has emerged as a potent strategy for enhancing tumor control; several classes of agents are described as potentially suitable for combination with mTOR inhibitors, e.g. everolimus.
Materials and methods: Controlled phase II/III clinical trials.
Conference: 7th Annual ENETSConcerence (2010)
Presenting Author:
Keywords: neuroendocrine tumors, mammalian target of rapamycin, somatostatin analogs, vascular endothelial growth factor, cytotoxic therapy, interferon-alpha, controlled clinical trials,
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