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Published on: February 3, 2023
Kinase Fusion-Related Thyroid Carcinomas: Towards Predictive Models for Advanced Actionable Diagnostics
Ying-Hsia Chu1, Peter M Sadow2
1Department of Pathology, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan.
Abstract:
The past decade has brought significant advances in our understanding of the molecular mechanisms of thyroid carcinogenesis. Among thyroid carcinomas, the most successful class of targeted therapeutics appears to be selective kinase inhibitors. Actionable kinase fusions arise in around 10-15% of cases of thyroid cancer, a significant subset. A cohort of molecular testing platforms, both commercial and laboratory-derived, has been introduced into clinical practice to identify patients with targetable tumors, requiring pathologists to develop an integrative approach that utilizes traditional diagnostic cytopathology and histopathology, immunohistochemistry, and cutting-edge molecular assays for optimal diagnostic, prognostic, and therapeutic efficiency. Furthermore, there has been increasing scrutiny of the clinical behavior of kinase fusion-driven thyroid carcinoma (KFTC), still regarded as papillary thyroid carcinomas, and in characterizing molecular predictors of kinase inhibitor resistance with an aim to establish standardized, evidence-based treatment regimens. This review presents an overview of the current literature on the clinicopathologic and molecular features of KFTC as well as the latest investigational progress and encountered challenges for this unique subset of thyroid neoplasias.
Insights
Targeted therapies, like kinase inhibitors, are effective for thyroid cancer with actionable kinase fusions. Understanding kinase fusion-driven thyroid carcinoma (KFTC) is crucial for effective treatment strategies.
Area of Science:
- Oncology
- Molecular Biology
- Pathology
Background:
- Thyroid cancer treatment has advanced with targeted therapies, particularly kinase inhibitors.
- Kinase fusions are found in 10-15% of thyroid cancers, representing a significant subset for targeted therapy.
- Molecular testing platforms are now integrated into clinical practice for identifying targetable tumors.
Purpose of the Study:
- To review the clinicopathologic and molecular features of kinase fusion-driven thyroid carcinoma (KFTC).
- To summarize current literature on KFTC, including investigational progress and challenges.
- To highlight the need for standardized, evidence-based treatment regimens for KFTC.
Main Methods:
- Review of current literature on KFTC.
- Analysis of clinicopathologic and molecular features.
- Examination of molecular predictors of kinase inhibitor resistance.
Main Results:
- Selective kinase inhibitors are a successful targeted therapy for a subset of thyroid carcinomas.
- An integrative approach combining traditional pathology and molecular assays is essential for diagnosis and treatment.
- Research is ongoing to characterize KFTC and identify resistance mechanisms.
Conclusions:
- Kinase fusion-driven thyroid carcinoma (KFTC) represents a unique and important subset of thyroid neoplasms.
- Further research is needed to establish standardized treatment regimens and overcome challenges in managing KFTC.
- Understanding molecular predictors of resistance is key to optimizing kinase inhibitor therapy.
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