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  • Title: Recent advances in the molecular pathogenesis and targeted therapies of medullary thyroid carcinoma.
    Author: Almeida MQ, Hoff AO.
    Journal: Curr Opin Oncol; 2012 May; 24(3):229-34. PubMed ID: 22343387.
    Abstract:
    PURPOSE OF REVIEW: This review will focus on the recent advances in molecular pathogenesis and targeted therapies for medullary thyroid carcinoma (MTC). Unlike hereditary MTC in which rearranged during transfection (RET) mutations are the most important precipitating events, in sporadic MTC the genetic or molecular biomarkers are yet to be established. RECENT FINDINGS: Targeted molecular therapies that inhibit RET and other tyrosine kinase receptors involved in angiogenesis have shown great promise in the treatment of metastatic or locally advanced MTC and are under investigation. In addition, the recent findings of H-RAS mutations in 56% of RET-negative sporadic MTC and the activation of the mammalian target of rapamycin (mTOR) intracellular signaling pathway in hereditary MTC suggests that additional or alternative genetic events are important for MTC pathogenesis. SUMMARY: Recently, vandetanib (ZD6474), an inhibitor of vascular endothelial growth factor receptor (VEGFR) 2 and VEGFR 3, RET, and epidermal growth factor receptor (EGFR), was approved for the treatment of adults with symptomatic or progressive MTC. Significant advantages for vandetanib over placebo were seen in terms of response rate, disease control rate, and biochemical response in a phase III study. Furthermore, cabozantinib (XL184), an inhibitor of VEGFR 1 and VEGFR 2, hepatocyte growth factor receptor (MET), and RET, was associated with partial response and stable disease in 29 and 41%, respectively.
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