Evolution of anaplastic thyroid cancer management: perspectives in the era of precision oncology

Abstract

Anaplastic thyroid cancer is a rare aggressive malignancy resulting in poor outcomes, including significant morbidity and mortality. Historically, the overall survival of patients with anaplastic thyroid cancer has been less than 12 months. Multidisciplinary approaches combining surgery, radiation, and chemotherapy have been implemented to control this ominous disease. The evolution in science and technology has promoted deeper knowledge in the genetic pathways and mechanisms driving advance thyroid cancer. Furthermore, understanding molecular pathways resulted in the application of antineoplastic agents used in other tumors to thyroid cancer and the development of new highly selective drugs. A major landmark in anaplastic thyroid cancer management history was recently reached with the approval of BRAF and MEK inhibitor combination, specifically dabrafenib and trametinib for BRAF-mutated anaplastic thyroid cancer; this treatment has improved survival and outcomes in this population. Similarly, newer kinase inhibitors and immunotherapy are further shifting advanced thyroid cancer management to consider as first-line therapy inhibiting actionable oncogenic alterations. Therefore, newer treatment paradigms are incorporating molecular testing to provide personalized cancer care in anaplastic thyroid cancer. In this review, the principal aim is to provide an overview of the available international data on tyrosine kinase inhibitors and immunotherapy in the management of anaplastic thyroid cancer.

Keywords: anaplastic thyroid cancer; dabrafenib; precision oncology; trametinib; tyrosine kinase inhibitors.

Figure 1.

Schematic review of cellular pathways targeted by oral antineoplastic agents in thyroid cancer. Tyrosine kinase receptors including vascular endothelial growth factor receptor (VEGFR), fibroblast growth factor receptor (FGFR), platelet-derived growth factor α (PDGFα), and RET can activate internal MAPK pathways which can lead to tumor proliferation; in a similar way, TRK and RET fusions can lead to tumorigenesis. The figure above highlights several multikinase inhibitors described in this article with their respective target receptors or fusions. In addition, dabrafenib and trametinib inhibit BRAF and MEK, respectively, from the MAPK pathway which has led to improvement in survival on BRAF-altered ATC cases.