Recent advances in anaplastic thyroid cancer management

Abstract

Purpose of review To summarize recent developments in the diagnosis and management of patients with anaplastic thyroid cancer (ATC). Recent findings An updated edition of the Classification of Endocrine and Neuroendocrine Tumors was released by the World Health Organization (WHO), in which squamous cell carcinoma of the thyroid are now a subtype of ATC. Broader access to next generation sequencing has allowed better understanding of the molecular mechanisms driving ATC and improved prognostication. BRAF-targeted therapies revolutionized the treatment of advanced/metastatic BRAFV600E-mutated ATC, offering significant clinical benefit and allowing better locoregional control of disease through the neoadjuvant approach. However, inevitable development of resistance mechanisms represents a major challenge. Addition of immunotherapy to BRAF/MEK inhibition has shown very promising results and significant improvement in survival outcomes. Summary Major advancements took place in the characterization and management of ATC in recent years, especially in patients with a BRAF V600E mutation. Still, no curative treatment is available, and options are limited once resistance to currently available BRAF-targeted therapies develops. Additionally, there is still a need for more effective treatments for patients without a BRAF mutation.

Update on current diagnosis and management of anaplastic thyroid carcinoma

“…The MEK gene has a close connection to the BRAF gene. Both are responsible for mitogen-activated protein kinase that promotes cell proliferation, tumor growth and angiogenesis[ 41 , 52 , 53 ]. Other mutations found involve the following genes: p53 in 63% of cases, RET , RAS ( KRAS , HRAS , NRAS ) in 22% of cases, TERT promoter in 75% of cases, PIK3CA in 18% of cases, EIF1AX in 14% of cases, PTEN in 14% of cases[ 6 , 24 , 50 ], and NESTIN , CCND1 , POU5F1 , MCL1 , MYBL2 , MCL1 , IQGAP1 , SOX2 , and NANOG [ 33 ].…”

“…Tumor removal increases the benefits of the treatment. In combination with radiation, new chemotherapy and novel gene targeted therapy can achieve locoregional disease control and improve survival and quality of life[ 36 , 41 , 53 , 65 , 67 ]. The guidelines of the National Comprehensive Cancer Network and ATA recommend surgical resection by lobectomy or near total thyroidectomy with wide lymphadenectomy in stage IVA and IVB, even in stage IVC when an R0 or at least R1 intervention could be achieved in locally resectable tumors[ 36 , 43 , 68 - 70 ].…”

“…The drugs for mechanisms of some implicated gene mutations include the following: (1) Angiogenesis-lenvatinib, sorafenib, sunitinib, vandetanib, combretastatin; (2) EGFR-docetaxel, gefitinib; (3) BRAF-dabrafenib, vemurafenib, encorafenib; and (4) MEK-trametinib, cobimetinib, binimetinib[ 24 ]. The combination of the BRAF inhibitor dabrafenib with the MEK inhibitor trametinib is the most widely used because it is considered more effective than each drug alone[ 6 , 24 , 41 , 82 , 83 ]. Combretastatin targets tumor vascularity.…”

“…Thus, it has been included in many research protocols. The existing immunotherapy regimens in combination with targeted therapy (dabrafenib - trametinib) can provide a further potential increase in effectiveness and improved survival benefits[ 41 , 91 , 92 ]. It is undoubted that the multimodality current treatment plan is accompanied by the best outcomes of this otherwise lethal disease[ 40 ].…”

“…This targeted therapy has been recommended as neoadjuvant treatment followed by surgery. It constitutes the standard care and ensures a two-year overall survival of 80%[ 4 , 24 , 40 , 41 ].…”