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THYROID CANCER IN 2019

Therapeutic breakthroughs for metastatic thyroid cancer

Nature Reviews Endocrinology volume 16, pages 77–78 (2020)Cite this article

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Multikinase inhibitors are effective treatments for thyroid cancers, acting primarily as antiangiogenic agents. This year, advances have been made in selective targeting of RET and BRAF in patients with medullary and anaplastic thyroid cancers, respectively. However, Hürthle cell carcinomas have a unique genomic landscape with no dominant truncal drivers, precluding simplistic approaches to therapeutic targeting.

Key advances

  • The combination of BRAF and MEK inhibition with dabrafenib and trametinib induces durable responses in patients with BRAFV600E-mutant anaplastic thyroid cancer, providing a road map for advancing the treatment of the most aggressive form of thyroid cancer2,4.

  • Two new selective RET inhibitors — BLU-667 and LOXO-292 — have potent antitumour effects in RET-mutant medullary thyroid carcinoma and RET-fusion papillary thyroid carcinomas, with a favourable safety profile5,6.

  • Hürthle cell carcinomas are a distinct entity characterized by mitochondrial dysfunction and widespread loss of heterozygosity9,10.

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Fig. 1: Highly selective versus promiscuous kinase driver inhibitors.

References

  1. Fagin, J. A. & Wells, S. A. Jr. Biologic and clinical perspectives on thyroid cancer. N. Engl. J. Med. 375, 2307 (2016).

    Article  Google Scholar 

  2. Subbiah, V. et al. Dabrafenib and trametinib treatment in patients with locally advanced or metastatic BRAF V600-mutant anaplastic thyroid cancer. J. Clin. Oncol. 36, 7–13 (2018).

    Article  CAS  Google Scholar 

  3. Shah, M. H. et al. Results of randomized phase II trial of dabrafenib versus dabrafenib plus trametinib in BRAF-mutated papillary thyroid carcinoma. J. Clin. Oncol. 35 (Suppl. 15), 6022 (2017).

    Article  Google Scholar 

  4. Wang, J. R. et al. Complete surgical resection following neoadjuvant dabrafenib plus trametinib in BRAF(V600E)-mutated anaplastic thyroid carcinoma. Thyroid 29, 1036–1043 (2019).

    Article  CAS  Google Scholar 

  5. Subbiah, V. et al. Precision targeted therapy with BLU-667 for RET-driven cancers. Cancer Discov. 8, 836–849 (2018).

    Article  CAS  Google Scholar 

  6. Subbiah, V. et al. Selective RET kinase inhibition for patients with RET-altered cancers. Ann. Oncol. 29, 1869–1876 (2018).

    Article  CAS  Google Scholar 

  7. Taylor, M. H. et al. Activity and tolerability of BLU-667, a highly potent and selective RET inhibitor, in patients with advanced RET-altered thyroid cancers [abstract]. J. Clin. Oncol. 37 (Suppl. 15), 6018 (2019).

    Article  Google Scholar 

  8. Wirth, L. J. et al. Registrational results of LOXO-292 in patients with RET-altered thyroid cancers [abstract]. Ann. Oncol. 30 (Suppl. 5), v851–v934 (2019).

    Google Scholar 

  9. Ganly, I. et al. Integrated genomic analysis of Hürthle cell cancer reveals oncogenic drivers, recurrent mitochondrial mutations, and unique chromosomal landscapes. Cancer Cell 34, 256–270 (2018).

    Article  CAS  Google Scholar 

  10. Gopal, R. K. et al. Widespread chromosomal losses and mitochondrial DNA alterations as genetic drivers in Hurthle cell carcinoma. Cancer Cell 34, 242–255 (2018).

    Article  CAS  Google Scholar 

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Acknowledgements

The authors are supported in part by NIH RO1-CA50706, NIH RO1-CA72597, NIH P50-CA72012 and P30-CA008748.

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Authors and Affiliations

  1. Department of Medicine and Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Vera Tiedje & James A. Fagin

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  1. Vera Tiedje
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Correspondence to James A. Fagin.

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Competing interests

J.A.F. has received consultancy fees from Loxo Oncology and a grant from Eisai. V.T. declares no competing interests.

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Tiedje, V., Fagin, J.A. Therapeutic breakthroughs for metastatic thyroid cancer. Nat Rev Endocrinol 16, 77–78 (2020). https://doi.org/10.1038/s41574-019-0307-2

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