Kinase gene fusions: roles and therapeutic value in progressive and refractory papillary thyroid cancer

J Cancer Res Clin Oncol. 2021 Feb;147(2):323-337. doi: 10.1007/s00432-020-03491-5. Epub 2021 Jan 2.

Abstract

The incidence of papillary thyroid cancer (PTC), the major type of thyroid cancer, is increasing rapidly around the world, and its pathogenesis is still unclear. There is poor prognosis for PTC involved in rapidly progressive tumors and resistance to radioiodine therapy. Kinase gene fusions have been discovered to be present in a wide variety of malignant tumors, and an increasing number of novel types have been detected in PTC, especially progressive tumors. As a tumor-driving event, kinase fusions are constitutively activated or overexpress their kinase function, conferring oncogenic potential, and their frequency is second only to BRAFV600E mutation in PTC. Diverse forms of kinase fusions have been observed and are associated with specific pathological features of PTC (usually at an advanced stage), and clinical trials of therapeutic strategies targeting kinase gene fusions are feasible for radioiodine-resistant PTC. This review summarizes the roles of kinase gene fusions in PTC and the value of clinical therapy of targeting fusions in progressive or refractory PTC, and discusses the future perspectives and challenges related to kinase gene fusions in PTC patients.

Keywords: Kinase gene fusions; Kinase inhibitors; Lymph node metastasis; Papillary thyroid cancer; Radioiodine refractory.

Publication types

  • Review

MeSH terms

  • Anaplastic Lymphoma Kinase / genetics
  • Gene Fusion* / drug effects
  • Gene Fusion* / physiology
  • Humans
  • Protein Kinase Inhibitors / therapeutic use
  • Protein Kinases / genetics*
  • Proto-Oncogene Proteins B-raf / genetics
  • Proto-Oncogene Proteins c-ret / genetics
  • Receptor, trkA / genetics
  • Thyroid Cancer, Papillary / drug therapy
  • Thyroid Cancer, Papillary / genetics*
  • Thyroid Neoplasms / drug therapy
  • Thyroid Neoplasms / genetics*

Substances

  • NTRK1 protein, human
  • Protein Kinase Inhibitors
  • Protein Kinases
  • ALK protein, human
  • Anaplastic Lymphoma Kinase
  • Proto-Oncogene Proteins c-ret
  • RET protein, human
  • Receptor, trkA
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf