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

Int J Mol Sci. 2020 Jul 13;21(14):4951. doi: 10.3390/ijms21144951.

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.

Publication types

  • Review

MeSH terms

  • Adenocarcinoma, Follicular / enzymology
  • Adenocarcinoma, Follicular / genetics
  • Adenocarcinoma, Follicular / therapy
  • Adenoma, Oxyphilic / enzymology
  • Adenoma, Oxyphilic / genetics
  • Adenoma, Oxyphilic / therapy
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Antineoplastic Agents, Immunological / therapeutic use
  • Carcinoma, Medullary / enzymology
  • Carcinoma, Medullary / genetics
  • Carcinoma, Medullary / therapy
  • Carcinoma, Papillary / enzymology
  • Carcinoma, Papillary / genetics
  • Carcinoma, Papillary / therapy
  • Clinical Trials as Topic
  • Combined Modality Therapy
  • Disease Management
  • Forecasting
  • Genes, Neoplasm
  • Humans
  • Immune Checkpoint Inhibitors / therapeutic use
  • Immunoconjugates / therapeutic use
  • Immunotherapy
  • Iodine Radioisotopes / therapeutic use
  • Molecular Targeted Therapy*
  • Multicenter Studies as Topic
  • Neoplasm Proteins / antagonists & inhibitors*
  • Neoplasm Proteins / genetics
  • Oncogene Proteins, Fusion / antagonists & inhibitors
  • Oncogene Proteins, Fusion / genetics
  • Protein Kinase Inhibitors / pharmacology
  • Protein Kinase Inhibitors / therapeutic use*
  • Protein-Tyrosine Kinases / antagonists & inhibitors*
  • Protein-Tyrosine Kinases / genetics
  • Randomized Controlled Trials as Topic
  • Thyroid Neoplasms / enzymology
  • Thyroid Neoplasms / genetics
  • Thyroid Neoplasms / therapy*
  • Tumor Microenvironment / immunology

Substances

  • Antineoplastic Agents
  • Antineoplastic Agents, Immunological
  • Immune Checkpoint Inhibitors
  • Immunoconjugates
  • Iodine Radioisotopes
  • Neoplasm Proteins
  • Oncogene Proteins, Fusion
  • Protein Kinase Inhibitors
  • Protein-Tyrosine Kinases