Current and Future Role of Tyrosine Kinases Inhibition in Thyroid Cancer: From Biology to Therapy

Abstract

Thyroid cancer represents a heterogenous disease whose incidence has increased in the last decades. Although three main different subtypes have been described, molecular characterization is progressively being included in the diagnostic and therapeutic algorithm of these patients. In fact, thyroid cancer is a landmark in the oncological approach to solid tumors as it harbors key genetic alterations driving tumor progression that have been demonstrated to be potential actionable targets. Within this promising and rapid changing scenario, current efforts are directed to improve tumor characterization for an accurate guidance in the therapeutic management. In this sense, it is strongly recommended to perform tissue genotyping to patients that are going to be considered for systemic therapy in order to select the adequate treatment, according to recent clinical trials data. Overall, the aim of this article is to provide a comprehensive review on the molecular biology of thyroid cancer focusing on the key role of tyrosine kinases. Additionally, from a clinical point of view, we provide a thorough perspective, current and future, in the treatment landscape of this tumor.

Keywords: NTRK; RET; immunotherapy; thyroid cancer; tyrosine kinase inhibitors.

Figure 1

Overview of the current treatment approach in MTC. In this figure, we illustrate several drugs targeting the main molecular pathways involved in MTC tumorigenesis (MAPK and PI3K/AKT/mTOR), with special focus on the latest advances in RET inhibition.

Figure 2

Overview of the current treatment approach in ATC. In this figure, we illustrate several drugs targeting the main molecular pathways involved in ATC tumorigenesis, with special focus on BRAF inhibition and immune checkpoint inhibitors.