Targeted Therapy for Thyroid Cancer: Striking the Survival Signaling

摘要

The genomic alterations C that characterize each tumor are responsible for both the initiation and maintenance of the malignancy. Genomic medicine, which uses information from genomes to treat diseases, is a rapidly advancing field that applies specifically to guiding the treatment of cancer. In each tumor, specific genetic alterations can be the site for tar- geted therapeutic agents. Theoretically, targeted therapy is better than systemic therapies with antitumor agents because it is more focused and thus can be more powerful and less toxic. Based on this principle, a number of new drugs have been developed to hit specific targets, such as tyrosine kinase receptors, kinases, and oncogenes. Although advanced cancer often has multiple genetic defects affecting diverse biochemical pathways, the sur- vival of cancer cells becomes dependent on the continued activation of particular oncogenes (the phenomenon of oncogene addiction). Accordingly, targeting this single ge- netic mutation deeply affects cell viability. As a case in point, growth arrest and apoptosis are induced by RAF inhibitors in melanoma cells bearing BRAF mutations in culture and in murine xenograft models (1). These pre- clinical findings supported mutant BRAF as an attractive target for melanoma therapy and for those tumors that frequently harbor BRAF mutations such as papillary thy- roid cancer (PTC). Many selective RAF inhibitors are cur- rently in clinical trials in different types of cancer, includ- ing melanoma, PTC, colorectal, and non-small-cell lung cancer. Although clinical studies of selective RAF inhibi- tors have shown encouraging results with frequent early tumor responses, in a relevant fraction of patients this effect is of short duration with frequent relapse or no re- sponse.