title: Dual inhibition of mTOR pathway and VEGF signalling in neuroendocrine neoplasms: from bench to bedside.
abstract: After years of limited progress in the treatment of neuroendocrine neoplasms (NENs), an increasing number of therapeutic targets have recently emerged as potential tools to improve disease outcome. The mammalian target of rapamycin (mTOR) pathway and vascular endothelial growth factor (VEGF) signalling are implicated in the regulation of cell growth, proliferation, neo-angiogenesis and tumour cell spread. Their combined blockade, in a simultaneous or sequential strategy, represents an intriguing biological rationale to overcome the onset of resistance mechanisms. However, is becoming increasingly imperative to find the optimal sequential strategy according to the best toxicity profile, and also to identify predictive biomarkers. We will provide an overview of the pre-clinical and clinical data relating to mTOR pathway/VEGF signalling as a potential targets of treatment in NENs.
authors.affiliation: Unit of Gastrointestinal Medical Oncology and Neuroendocrine Tumors, European Institute of Oncology, Milan, Italy; Department of Experimental Oncology, European Institute of Oncology, Milan, Italy; Department of Biosciences, University of Milan, Italy.
authors.forename: Chiara Alessandra
authors.initials: CA
authors.lastname: Cella
authors.affiliation: Unit of Gastrointestinal Medical Oncology and Neuroendocrine Tumors, European Institute of Oncology, Milan, Italy; Department of Experimental Oncology, European Institute of Oncology, Milan, Italy; Department of Biosciences, University of Milan, Italy.
authors.forename: Saverio
authors.initials: S
authors.lastname: Minucci
authors.affiliation: Unit of Gastrointestinal Medical Oncology and Neuroendocrine Tumors, European Institute of Oncology, Milan, Italy; Department of Experimental Oncology, European Institute of Oncology, Milan, Italy; Department of Biosciences, University of Milan, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Spada
authors.affiliation: Unit of Gastrointestinal Medical Oncology and Neuroendocrine Tumors, European Institute of Oncology, Milan, Italy; Department of Experimental Oncology, European Institute of Oncology, Milan, Italy; Department of Biosciences, University of Milan, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Galdy
authors.affiliation: Unit of Gastrointestinal Medical Oncology and Neuroendocrine Tumors, European Institute of Oncology, Milan, Italy; Department of Experimental Oncology, European Institute of Oncology, Milan, Italy; Department of Biosciences, University of Milan, Italy.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Elgendy
authors.affiliation: Unit of Gastrointestinal Medical Oncology and Neuroendocrine Tumors, European Institute of Oncology, Milan, Italy; Department of Experimental Oncology, European Institute of Oncology, Milan, Italy; Department of Biosciences, University of Milan, Italy.
authors.forename: Paola Simona
authors.initials: PS
authors.lastname: Ravenda
authors.affiliation: Unit of Gastrointestinal Medical Oncology and Neuroendocrine Tumors, European Institute of Oncology, Milan, Italy; Department of Experimental Oncology, European Institute of Oncology, Milan, Italy; Department of Biosciences, University of Milan, Italy.
authors.forename: Maria Giulia
authors.initials: MG
authors.lastname: Zampino
authors.affiliation: Unit of Gastrointestinal Medical Oncology and Neuroendocrine Tumors, European Institute of Oncology, Milan, Italy; Department of Experimental Oncology, European Institute of Oncology, Milan, Italy; Department of Biosciences, University of Milan, Italy.
authors.forename: Sabina
authors.initials: S
authors.lastname: Murgioni
authors.affiliation: Unit of Gastrointestinal Medical Oncology and Neuroendocrine Tumors, European Institute of Oncology, Milan, Italy; Department of Experimental Oncology, European Institute of Oncology, Milan, Italy; Department of Biosciences, University of Milan, Italy. Electronic address: nicola.fazio@ieo.it.
authors.forename: Nicola
authors.initials: N
authors.lastname: Fazio
mesh_terms: D043925:Angiogenesis Inducing Agents / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology* / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D004357:Drug Synergism; D006801:Humans; D007211:Indoles / Q000008:administration & dosage / Q000494:pharmacology; D058990:Molecular Targeted Therapy; D018358:Neuroendocrine Tumors / Q000188:drug therapy* / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D011758:Pyrroles / Q000008:administration & dosage / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D000077210:Sunitinib; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D057170:Translational Research, Biomedical; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D043925:Angiogenesis Inducing Agents; D007211:Indoles; D047428:Protein Kinase Inhibitors; D011758:Pyrroles; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D000077210:Sunitinib
keywords: Dual inhibition; Hypoxia; Neuroendocrine tumours; VEGF signalling; mTOR pathway