Abstract
The REarranged during Transfection (RET) proto-oncogene and its activated signalling pathways have been shown to play an important role in cancer. RET genetic alterations including germline, somatic mutations and gene rearrangements have been demonstrated in several solid tumours, and numerous clinical trials using multikinase inhibitors containing RET as a target have shown significant activity against RET. Sorafenib and sunitinib have been approved for the treatment of renal, hepatocellular, gastrointestinal and pancreatic neuoendocrine carcinomas. Vandetanib has recently been approved for the treatment of unresectable locally advanced or metastatic medullary thyroid carcinomas. Novel genomic rearrangements and RET signalling interactions are now being studied in a variety of tumours and will provide the basis for new therapeutic strategies. Combination or sequential targeted therapies that are based on solid preclinical data regarding the inhibition of RET-mediated parallel or different -signalling pathways will likely be more effective.
Keywords: RET proto-oncogene, cancer, RET-activated signalling pathways, RET interacting proteins, tyrosine kinase inhibitors, targeted therapies, clinical trials, therapeutic strategies, sorafenib, sunitinib
Current Pharmaceutical Design
Title:Inhibition of RET Activated Pathways: Novel Strategies for Therapeutic Intervention in Human Cancers
Volume: 19 Issue: 5
Author(s): Libero Santarpia and Giulia Bottai
Affiliation:
Keywords: RET proto-oncogene, cancer, RET-activated signalling pathways, RET interacting proteins, tyrosine kinase inhibitors, targeted therapies, clinical trials, therapeutic strategies, sorafenib, sunitinib
Abstract: The REarranged during Transfection (RET) proto-oncogene and its activated signalling pathways have been shown to play an important role in cancer. RET genetic alterations including germline, somatic mutations and gene rearrangements have been demonstrated in several solid tumours, and numerous clinical trials using multikinase inhibitors containing RET as a target have shown significant activity against RET. Sorafenib and sunitinib have been approved for the treatment of renal, hepatocellular, gastrointestinal and pancreatic neuoendocrine carcinomas. Vandetanib has recently been approved for the treatment of unresectable locally advanced or metastatic medullary thyroid carcinomas. Novel genomic rearrangements and RET signalling interactions are now being studied in a variety of tumours and will provide the basis for new therapeutic strategies. Combination or sequential targeted therapies that are based on solid preclinical data regarding the inhibition of RET-mediated parallel or different -signalling pathways will likely be more effective.
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Cite this article as:
Santarpia Libero and Bottai Giulia, Inhibition of RET Activated Pathways: Novel Strategies for Therapeutic Intervention in Human Cancers, Current Pharmaceutical Design 2013; 19 (5) . https://dx.doi.org/10.2174/1381612811306050864
DOI https://dx.doi.org/10.2174/1381612811306050864 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
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