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Published on: January 29, 2019
An Update on Redifferentiation Therapy for Radioiodine Refractory Thyroid Cancer
1Department of Medicine, Endocrinology Service, Memorial Sloan Kettering Cancer Center - Weill Cornell Medical College, 530 East 74th Street, Suite 22244, New York, NY 10021, USA.
Abstract:
Two-thirds of patients with advanced thyroid cancer are refractory to radioactive iodine (RAI). Inhibition of genetic drivers of thyroid cancer in the intracellular mitogen-activated protein kinase pathway, like BRAF, RAS, RET, and NTRK, results in increased expression of thyroid differentiation genes and the sodium-iodine symporter. Targeted therapies in combination with RAI result in structural decrease of metastatic lesions in 33% to 63% of patients that successfully take up RAI after redifferentiation. The true efficacy of targeted therapies with RAI remains to be proven in clinical trials against the efficacy of targeted therapies without RAI or against multi-kinase inhibitors.
Insights
Targeted therapies can re-sensitize advanced thyroid cancer to radioactive iodine (RAI) treatment by inhibiting key genetic drivers. Further clinical trials are needed to confirm the efficacy of targeted therapies combined with RAI.
Area of Science:
- Oncology
- Molecular Biology
- Radiopharmaceutical Therapy
Background:
- Two-thirds of advanced thyroid cancer patients do not respond to radioactive iodine (RAI) therapy.
- Targeting specific genetic drivers in the mitogen-activated protein kinase pathway is crucial for thyroid cancer treatment.
Purpose of the Study:
- To investigate the potential of targeted therapies to re-sensitize RAI-refractory thyroid cancer.
- To evaluate the impact of targeted therapies on the expression of thyroid differentiation genes and the sodium-iodine symporter.
Main Methods:
- Inhibition of genetic drivers (BRAF, RAS, RET, NTRK) within the mitogen-activated protein kinase pathway.
- Assessment of targeted therapy efficacy in combination with RAI for metastatic lesions.
Main Results:
- Targeted therapy inhibition leads to increased expression of thyroid differentiation genes and the sodium-iodine symporter.
- Combination of targeted therapies with RAI showed a 33% to 63% reduction in metastatic lesions in responsive patients.
Conclusions:
- Targeted therapies show promise in restoring RAI uptake in advanced thyroid cancer.
- Clinical trials are necessary to compare the efficacy of targeted therapies with RAI versus targeted therapies alone or multi-kinase inhibitors.
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