Dual inhibition of mTOR pathway and VEGF signalling in neuroendocrine neoplasms: from bench to bedside

Chiara Alessandra Cella; Saverio Minucci; Francesca Spada; Salvatore Galdy; Mohamed Elgendy; Paola Simona Ravenda; Maria Giulia Zampino; Sabina Murgioni; Nicola Fazio

doi:10.1016/j.ctrv.2015.06.008

Dual inhibition of mTOR pathway and VEGF signalling in neuroendocrine neoplasms: from bench to bedside

Cancer Treat Rev. 2015 Nov;41(9):754-60. doi: 10.1016/j.ctrv.2015.06.008. Epub 2015 Jun 28.

Authors

Chiara Alessandra Cella¹, Saverio Minucci¹, Francesca Spada¹, Salvatore Galdy¹, Mohamed Elgendy¹, Paola Simona Ravenda¹, Maria Giulia Zampino¹, Sabina Murgioni¹, Nicola Fazio²

Affiliations

¹ 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.
² 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: [email protected].

PMID: 26142874
DOI: 10.1016/j.ctrv.2015.06.008

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.

Keywords: Dual inhibition; Hypoxia; Neuroendocrine tumours; VEGF signalling; mTOR pathway.

Publication types

Review

MeSH terms

Angiogenesis Inducing Agents / administration & dosage
Angiogenesis Inducing Agents / pharmacology*
Animals
Antineoplastic Combined Chemotherapy Protocols / pharmacology*
Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
Clinical Trials as Topic
Drug Synergism
Humans
Indoles / administration & dosage
Indoles / pharmacology
Molecular Targeted Therapy
Neuroendocrine Tumors / drug therapy*
Neuroendocrine Tumors / metabolism
Protein Kinase Inhibitors / administration & dosage
Protein Kinase Inhibitors / pharmacology*
Pyrroles / administration & dosage
Pyrroles / pharmacology
Signal Transduction / drug effects
Sunitinib
TOR Serine-Threonine Kinases / antagonists & inhibitors*
TOR Serine-Threonine Kinases / metabolism
Translational Research, Biomedical
Vascular Endothelial Growth Factor A / antagonists & inhibitors*
Vascular Endothelial Growth Factor A / metabolism

Substances

Angiogenesis Inducing Agents
Indoles
Protein Kinase Inhibitors
Pyrroles
VEGFA protein, human
Vascular Endothelial Growth Factor A
MTOR protein, human
TOR Serine-Threonine Kinases
Sunitinib