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Updated: Nov 17, 2025
An Orthotopic Mouse Model of Anaplastic Thyroid Carcinoma
Published on: April 17, 2013
Molecular-Driven Therapy in Advanced Thyroid Cancer
Kevin C Miller1, Ashish V Chintakuntlawar2
1Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.
Opinion Statement:
With a growing understanding of the biologic drivers of different thyroid cancers, there is an ongoing revolution in the treatment of aggressive and advanced disease variants. This includes matching patients with specific point mutations or gene fusions to targeted therapies (e.g., selective RET inhibitors), delineating patients who are likely to respond to immune checkpoint inhibition (i.e., PD-L1-positive tumors) and even priming responses to traditional therapies such as radioactive iodine (via concomitant MAPK pathway inhibition). There is also a growing role for genomics in the prognostication of thyroid tumors to aid the adjudication of appropriate treatments. Taking stock of the current state of the field, recent successes should be celebrated, but there still remains a long road ahead to improve outcomes for patients, particularly for radioactive-iodine refractory differentiated thyroid cancer and anaplastic thyroid cancer. In this review, we summarize findings from recent clinical trials and highlight promising preclinical data supporting molecular-driven therapy in advanced thyroid cancer. Ultimately, enrollment in clinical trials remains paramount to the advancement of thyroid cancer care.
Insights
Targeted therapies and genomics are revolutionizing advanced thyroid cancer treatment by matching patients to specific treatments. Further research and clinical trial enrollment are crucial for improving outcomes in refractory and anaplastic thyroid cancers.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- Understanding the molecular drivers of thyroid cancer has led to significant advancements in treating aggressive and advanced disease.
- Current treatment strategies involve matching patients to targeted therapies based on specific mutations or gene fusions.
- Genomic profiling plays an increasing role in prognostication to guide treatment decisions.
Purpose of the Study:
- To review recent clinical trial findings and preclinical data on molecular-driven therapies for advanced thyroid cancer.
- To highlight successes and remaining challenges in the field.
- To emphasize the importance of clinical trial participation for advancing patient care.
Main Methods:
- Review of recent clinical trials in advanced thyroid cancer.
- Summary of promising preclinical data supporting molecular-targeted therapies.
- Discussion of the role of genomics in prognostication and treatment selection.
Main Results:
- Targeted therapies, such as selective RET inhibitors, show promise for specific patient subsets.
- Immune checkpoint inhibitors are being investigated for PD-L1-positive tumors.
- MAPK pathway inhibition may enhance responses to radioactive iodine therapy.
- Genomic insights are improving prognostication for thyroid tumors.
Conclusions:
- Molecular-driven therapies represent a paradigm shift in advanced thyroid cancer treatment.
- Despite progress, significant challenges remain, particularly for radioactive-iodine refractory differentiated thyroid cancer and anaplastic thyroid cancer.
- Continued research and enrollment in clinical trials are essential for improving patient outcomes.
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