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.
