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New therapeutic approaches to treat medullary thyroid carcinoma

Abstract

Medullary thyroid carcinoma (MTC) accounts for up to 8% of all thyroid cancers. Although primary surgery is curative in the vast majority of patients treated at an early stage, disease can persist or recur with deleterious effects on quality of life. Local and distant metastases can occur and are the major causes of mortality. Reoperation, embolization, and perhaps radiotherapy can improve the outcome for some patients who are not cured by primary surgery, but there is a need for novel treatments. No comprehensive clinical trial data are available on conventional cytotoxic agents for the treatment of MTC. Patients with distant metastases, in particular, might benefit from several novel compounds directed against angiogenesis and molecular targets in tumor cells, such as products of the proto-oncogene RET and mutants of it, and other signaling components. Well-conducted clinical trials are needed to assess and optimize these treatment strategies, and this article outlines how such trials should be conducted. Although RET mutations are common in hereditary MTC and can occur in some cases of sporadic MTC, knowledge of other molecular defects associated with the development of MTC should reveal new targets for therapy.

Key Points

  • Most cases of medullary thyroid carcinoma (MTC) are cured by initial surgery when this is performed at an early stage

  • Disease can persist or recur and metastasis can occur, with potentially serious effects on quality of life and mortality

  • New drugs that rely on knowledge of molecular oncology in MTC are available and are especially needed for patients with metastatic MTC

  • Well-designed clinical trials should be informative to select the most-active compounds among existing and novel treatment modalities

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Figure 1: The structure and functions of RET.

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Acknowledgements

Désirée Lie, University of California, Irvine, CA, is the author of and is solely responsible for the content of the learning objectives, questions and answers of the Medscape-accredited continuing medical education activity associated with this article.

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Correspondence to Martin Schlumberger.

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Competing interests

M Schlumberger and JM Bidart have received research grants from Amgen and AstraZeneca. F Carlomagno and M Santoro have received research grants from Amgen, AstraZeneca and Bayer Pharmaceuticals. E Baudin declared no competing interests.

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Schlumberger, M., Carlomagno, F., Baudin, E. et al. New therapeutic approaches to treat medullary thyroid carcinoma. Nat Rev Endocrinol 4, 22–32 (2008). https://doi.org/10.1038/ncpendmet0717

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