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Moreover, environmental exposure to radiation also induces rearranged transforming RET \u201cisoforms\u201d that are found in papillary thyroid cancer. The\n                    <jats:italic>RET<\/jats:italic>\n                    gene codes for a tyrosine kinase receptor that targets a diverse set of intracellular signaling pathways. The nature of\n                    <jats:italic>RET<\/jats:italic>\n                    point mutations predicts differences in the mechanisms by which the receptor becomes activated and correlates with different forms of clinical presentation, age of onset, and biological aggressiveness. A number of RET-targeting Tyrosine Kinase Inhibitors (TKIs) are currently undergoing clinical trials to evaluate their effectiveness in the treatment of thyroid cancer, and it is conceivable that the RET genotype may also influence response to these compounds. The question that now emerges is whether, in the future, the rational for treatment of refractory thyroid cancer will be based on the management of an abnormal RET signal. In this paper we address the RET-targeting TKIs and review studies about the signaling properties of distinct RET mutants as a means to predict response and design combinatorial therapies for the soon to be available TKIs.\n                  <\/jats:p>","DOI":"10.4061\/2011\/678357","type":"journal-article","created":{"date-parts":[[2011,6,26]],"date-time":"2011-06-26T13:14:09Z","timestamp":1309094049000},"page":"1-10","source":"Crossref","is-referenced-by-count":13,"title":["How to Treat a Signal? 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