Potential synergies for combined targeted therapy in the treatment of neuroendocrine cancer Journal Article


Authors: Salazar, R.; Reidy-Lagunes, D.; Yao, J.
Article Title: Potential synergies for combined targeted therapy in the treatment of neuroendocrine cancer
Abstract: Well differentiated neuroendocrine tumours (WDNET) are a diverse group of cancers that are often advanced at the time of diagnosis and generally do not respond significantly to traditional chemotherapy. A number of intriguing therapeutic targets have emerged, including somatostatin receptors, insulin-like growth factor-1 (IGF-1) and its receptor (IGF-1R), the phosphatidylinositol 3-kinase (PI3K)Aktmammalian target of rapamycin (mTOR) pathway, and vascular endothelial growth factor receptor. Functional somatostatin receptors and IGF-1R as well as dysregulated mTOR a key pathway component for both growth factor signalling and protein synthesis have been identified in human neuroendocrine tumour (NET) cell lines. Somatostatin analogues (SSA) and mTOR inhibitors have exhibited in vitro and in vivo antitumour activity against NET and have shown effects on the IGF-1 pathway in preclinical studies. SSA inhibit PI3KAkt signalling upstream of mTOR, suggesting that the combination of an SSA and an mTOR inhibitor may have greater efficacy than either as single agents. Recent clinical trial experience has provided some encouraging findings and prompted the design of additional studies of this dual-targeted approach to treating advanced WDNET. Results of ongoing trials of dual-targeted therapy combinations will define future therapies for advanced WDNET. © 2011 Adis Data Information BV. All rights reserved.
Keywords: sunitinib; temsirolimus; octreotide; everolimus; dalotuzumab; pasireotide; neuroendocrine-tumours
Journal Title: Drugs
Volume: 71
Issue: 7
ISSN: 0012-6667
Publisher: Adis International Ltd  
Date Published: 2011-05-07
Start Page: 841
End Page: 852
Language: English
DOI: 10.2165/11585500-000000000-00000
PROVIDER: scopus
PUBMED: 21568362
DOI/URL:
Notes: --- - "Export Date: 23 June 2011" - "CODEN: DRUGA" - "Source: Scopus"
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  1. Diane Lauren Reidy
    294 Reidy