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.
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Abbreviations
- PTC:
-
Papillary thyroid cancer
- DTC:
-
Differentiated thyroid cancer
- RAI:
-
Radioiodine
- RNA-seq:
-
Transcriptome level of sequencing
- TCGA:
-
The Cancer Genome Atlas
- RTK:
-
Receptor tyrosine kinase
- CC domain:
-
Coiled-coil domain
- LisH:
-
Lis1 homology
- SAM:
-
Sterile alpha motif
- S/TK:
-
Serine/threonine kinase
- RBD:
-
Ras-GTP binding domain
- FNAC:
-
Fine needle aspiration cytology
- PPV:
-
Positive predictive value
- NIFTP:
-
Noninvasive follicular thyroid neoplasm with papillary-like nuclear features
- TKI:
-
Tyrosine kinase inhibitor
- FGFR1-4:
-
Fibroblast growth factor receptors1-4
- PDGFRα:
-
Platelet-derived growth factor receptor α
- ORR:
-
Objective response rate
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This work was supported by grants from the National Natural Science Foundation of China (81974423, 81902729), the Key Research and Development Programme of Hunan Province (2019SK2031), the Natural Science Foundation of Hunan Province of China (2020JJ5904) and China Postdoctoral Science Foundation (2020M672517).
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Conceptualization, P.H. and S.C.; Resources, M.L., P.C., H.H., D.O., R.K., and H.T.; Data Curation, P.C., H.H., D.O., R.K., and H.T.; Writing, M.L. and P.H.; Supervision, P.H. and S.C.; Funding Acquisition, P.H. and S.C.
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Liu, M., Chen, P., Hu, HY. et al. Kinase gene fusions: roles and therapeutic value in progressive and refractory papillary thyroid cancer. J Cancer Res Clin Oncol 147, 323–337 (2021). https://doi.org/10.1007/s00432-020-03491-5
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DOI: https://doi.org/10.1007/s00432-020-03491-5