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Updated: Jul 10, 2025
Computer-Aided Three-Dimensional Visualization in the Treatment of Locally Advanced Thyroid Cancer
Published on: June 9, 2023
The Evolving Treatment Landscape of Medullary Thyroid Cancer
Marta Laganà1, Valentina Cremaschi1, Andrea Alberti2
1Medical Oncology Unit, Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia at ASST Spedali Civili, 25123, Brescia, Italy.
Opinion Statement:
Genetic assessment is crucial to address the correct treatment for advanced medullary thyroid cancer (MTC). Multi tyrosine kinase inhibitors (mTKIs) cabozantinib and vandetanib are good first line options, even vandetanib prescription is currently limited to RET mutated patients. Selective RET inhibitors such as pralsetinib could be a preferred upfront treatment in case of RET mutated MTC presenting common or gatekeeper RET mutations (e.g. M918T; V804L/M). Selpercatinib, otherwise, can be prescribed as the second line after disease progression to mTKIs. The best option for subsequent lines is to consider inclusion in clinical trials or alternatively other mTKIs such as sunitinib, sorafenib, lenvatinib, or pazopanib could be evaluated. New perspectives include next-generation RET inhibitors able to overcome resistance mechanisms responsible for disease progression to standard mTKIs and RET inhibitors, and immunotherapy for MTC presenting with high tumor mutational burden.
Insights
Genetic testing guides advanced medullary thyroid cancer (MTC) treatment. Targeted therapies like RET inhibitors and multi-tyrosine kinase inhibitors (mTKIs) offer effective options based on specific genetic mutations.
Area of Science:
- Oncology
- Genetics
- Pharmacology
Background:
- Advanced medullary thyroid cancer (MTC) treatment decisions are increasingly guided by genetic profiling.
- Current therapies include multi-tyrosine kinase inhibitors (mTKIs) and selective RET inhibitors, with varying efficacy based on RET mutation status.
Purpose of the Study:
- To outline the current landscape and future perspectives of targeted therapies for advanced medullary thyroid cancer (MTC).
- To emphasize the importance of genetic assessment in guiding treatment selection for MTC patients.
Main Methods:
- Review of current clinical guidelines and emerging research on targeted therapies for MTC.
- Analysis of the roles of multi-tyrosine kinase inhibitors (mTKIs) and selective RET inhibitors (e.g., pralsetinib, selpercatinib).
Main Results:
- Vandetanib and cabozantinib are first-line mTKIs, with vandetanib restricted to RET-mutated MTC.
- Selective RET inhibitors like pralsetinib are preferred for common/gatekeeper RET mutations upfront; selpercatinib is a second-line option post-mTKIs.
- Subsequent lines may involve clinical trials, other mTKIs, or immunotherapy for high tumor mutational burden MTC.
Conclusions:
- Genetic assessment is paramount for optimizing advanced MTC treatment strategies.
- A sequential approach utilizing mTKIs and selective RET inhibitors, guided by mutation status, is recommended.
- Future directions include next-generation inhibitors and immunotherapy to overcome resistance and improve outcomes.
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