Related Experiment Video
Updated: Sep 18, 2025
Spontaneous Murine Model of Anaplastic Thyroid Cancer
Published on: February 3, 2023
Characterization of Advanced RAS-driven Follicular-derived Thyroid Cancers and Review of Future Therapeutic Avenues
Sarah Hamidi1, Anastasios Maniakas2, Neal S Akhave3
1Department of Endocrine Neoplasia and Hormonal Disorders, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Context:
With novel RAS-targeted therapies emerging, better understanding of RAS-driven differentiated (DTC) and anaplastic (ATC) thyroid cancers is warranted.
Objective:
Characterize the genotypic and phenotypic landscape of RAS-driven DTC and ATC and review current and future therapeutic avenues.
Design:
Retrospective chart review between January 2015 and June 2023. Median follow-up duration 8.4 years in DTC cohort and 36.4 months in ATC cohort.
Setting:
Single-center study at MD Anderson Cancer Center.
Patients:
Individuals with RAS-altered DTC or ATC identified before kinase inhibitor exposure.
Interventions:
None.
Main Outcome Measures:
Primary objective was to describe clinical and molecular characteristics. Secondary objectives included identifying prognostic factors and assessing survival outcomes with available therapies.
Results:
Among 120 RAS-driven DTC and 71 RAS-driven ATC, NRAS was the most common alteration (69% of DTC, 70% of ATC), mainly at residue Q61. Brain metastases were found in 22% of patients undergoing brain imaging (19% in DTC, 25% in ATC). Median overall survival (OS) was 15.2 years in DTC, with 49% of patients receiving at least 1 line of systemic therapy, most commonly lenvatinib (66%). Median time to systemic therapy was 3.5 years from diagnosis, and median OS from therapy initiation was 6.0 years. In ATC, median OS was 7.5 months. Stage IVC [hazard ratio (HR) = 6.78)], neck surgery (HR = 0.29), and exposure to immunotherapy (HR = 0.13) were significantly associated with mortality.
Conclusion:
Advanced RAS-driven follicular-derived thyroid cancers seem to exhibit an aggressive behavior, particularly in ATC, in which prognosis remains poor despite expert multidisciplinary care. Advances in RAS-targeted therapies offer hope for improved therapeutic options.
Insights
RAS-driven thyroid cancers, particularly anaplastic thyroid cancer (ATC), show aggressive behavior. Novel RAS-targeted therapies offer potential for improved outcomes in these challenging differentiated thyroid cancer (DTC) and ATC cases.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Emerging novel RAS-targeted therapies necessitate a deeper understanding of RAS-driven differentiated thyroid cancer (DTC) and anaplastic thyroid cancer (ATC).
- RAS alterations are implicated in thyroid cancer pathogenesis, driving the need for comprehensive characterization.
Purpose of the Study:
- To characterize the genotypic and phenotypic landscape of RAS-driven DTC and ATC.
- To review current and future therapeutic avenues for these thyroid cancer subtypes.
Main Methods:
- Retrospective chart review of patients with RAS-altered DTC or ATC between January 2015 and June 2023.
- Single-center study at MD Anderson Cancer Center.
- Analysis included clinical and molecular characteristics, prognostic factors, and survival outcomes.
Main Results:
- NRAS was the most common RAS alteration (69% DTC, 70% ATC), primarily at residue Q61.
- Brain metastases occurred in 22% of patients imaged.
- Median overall survival (OS) was 15.2 years for DTC and 7.5 months for ATC. Stage IVC, neck surgery, and immunotherapy exposure were significant mortality predictors in ATC.
Conclusions:
- RAS-driven follicular-derived thyroid cancers, especially ATC, exhibit aggressive behavior with a poor prognosis despite multidisciplinary care.
- Advances in RAS-targeted therapies present a promising avenue for improving treatment options and patient outcomes.
Related Concept Videos
02:57Targeted Cancer Therapies
There are several types of targeted therapies against...
02:23Abnormal Proliferation
02:38The Ras Gene
Ras is a...
01:20Synthesis and Regulation of Thyroid Hormones
Upon reaching the thyroid gland, TSH stimulates the follicular cells' active uptake of iodide ions from the blood. The ions diffuse to the apical surface of the cells and are oxidized to iodine. The...