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.
This is a preview of subscription content, access via your institution
Access options
Access Nature and 54 other Nature Portfolio journals
Get Nature+, our best-value online-access subscription
$29.99 / 30 days
cancel any time
Subscribe to this journal
Receive 12 print issues and online access
$209.00 per year
only $17.42 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
References
Fagin, J. A. & Wells, S. A. Jr. Biologic and clinical perspectives on thyroid cancer. N. Engl. J. Med. 375, 2307 (2016).
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).
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).
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).
Subbiah, V. et al. Precision targeted therapy with BLU-667 for RET-driven cancers. Cancer Discov. 8, 836–849 (2018).
Subbiah, V. et al. Selective RET kinase inhibition for patients with RET-altered cancers. Ann. Oncol. 29, 1869–1876 (2018).
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).
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).
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).
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).
Acknowledgements
The authors are supported in part by NIH RO1-CA50706, NIH RO1-CA72597, NIH P50-CA72012 and P30-CA008748.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Competing interests
J.A.F. has received consultancy fees from Loxo Oncology and a grant from Eisai. V.T. declares no competing interests.
Rights and permissions
About this article
Cite this article
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
Published:
Issue Date:
DOI: https://doi.org/10.1038/s41574-019-0307-2