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Updated: Oct 30, 2025

Establishment and Characterization of Patient-Derived Xenograft Models of Anaplastic Thyroid Carcinoma and Head and Neck Squamous Cell Carcinoma
Published on: June 2, 2023
Kinase Inhibitors in the Treatment of Thyroid Cancer: Institutional Experience
Matea Pešorda1, Sanja Kusačić Kuna1, Dražen Huić1
11Clinical Department of Nuclear Medicine and Radiation Protection, Zagreb University Hospital Centre, Zagreb, Croatia; 2Clinical Department of Oncology, Zagreb University Hospital Centre, Zagreb, Croatia; 3The University of Zagreb School of Medicine, Zagreb, Croatia; 4The University of Zagreb School of Dental Medicine, Zagreb, Croatia.
Abstract:
Although most patients with thyroid cancer have a favorable clinical course, some patients develop a more aggressive type of cancer and exhibit more rapid disease progression with worse prognosis. Those patients usually exhibit mutations of proteins such as tyrosine kinase enzymes that play a significant role in regulation of tumor proliferation and spreading. Development of targeted therapies is based on the inhibition of mutated kinases which are involved in the MAPK signaling pathway. The aim of this study was to present the initial results of clinical experience with kinase inhibitors in patients with metastatic differentiated thyroid cancer (DTC), poorly differentiated thyroid cancer (PDTC), and medullary thyroid cancer (MTC) who exhibited rapid disease progression. A total of 17 adult patients (11 women, mean age 53.3 years) managed for progressive, metastatic disease were included in the study. Twelve patients with DTC and PDTC were previously tested for BRAF mutations, of whom nine that had tumor tissue negative for the BRAF V600E mutation received sorafenib, while three patients with tumors harboring the BRAF V600E mutation were treated with vemurafenib. Patients with MTC were treated with sunitinib, vandetanib, and sorafenib. Two patients with tumors harboring the BRAF mutation treated with vemurafenib showed restoration of radioiodine uptake. Most of patients showed significant improvement in disease status but of limited duration until disease progression. Although there was an improvement in progression-free survival, future research has to achieve a greater and longer-lasting response, probably by utilizing combined targeted therapy.
Insights
Targeted therapies like kinase inhibitors show promise for aggressive thyroid cancer. While improving progression-free survival, further research is needed for longer-lasting responses in metastatic differentiated, poorly differentiated, and medullary thyroid cancer.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Aggressive thyroid cancer subtypes, including differentiated (DTC), poorly differentiated (PDTC), and medullary (MTC), present significant clinical challenges.
- Mutated tyrosine kinases regulating tumor proliferation and spread are key drivers in aggressive thyroid cancer.
- Targeted therapies inhibiting kinases within the MAPK signaling pathway offer a therapeutic strategy.
Purpose of the Study:
- To evaluate the initial clinical outcomes of kinase inhibitors in patients with advanced, progressive thyroid cancer.
- To assess the efficacy of targeted therapies in metastatic DTC, PDTC, and MTC.
- To explore the impact of BRAF mutations on treatment response.
Main Methods:
- Retrospective analysis of 17 adult patients with progressive, metastatic thyroid cancer.
- Treatment with sorafenib, vemurafenib, sunitinib, or vandetanib based on cancer subtype and BRAF mutation status.
- Assessment of tumor response, including radioiodine uptake and progression-free survival.
Main Results:
- Two patients with BRAF-mutated tumors treated with vemurafenib demonstrated restored radioiodine uptake.
- Most patients experienced significant, albeit temporary, improvements in disease status.
- An overall improvement in progression-free survival was observed.
Conclusions:
- Kinase inhibitors provide a potential treatment avenue for aggressive thyroid cancer subtypes.
- BRAF mutation status influences treatment selection and response.
- Combined targeted therapy approaches may be necessary to achieve durable responses and improved long-term outcomes.
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