Follicular Thyroid Cancer (FTC) is a critical area of focus within oncology, demanding rigorous preclinical development to identify and validate effective therapeutic strategies. Protheragen is committed to advancing FTC diagnostics and therapeutics through our comprehensive suite of services.
Overview of Follicular Thyroid Cancer (FTC)
Follicular Thyroid Cancer (FTC) is the second most common type of thyroid malignancy, accounting for approximately 10-15% of all thyroid cancers. Arising from the follicular cells of the thyroid gland, FTC is characterized by its tendency to metastasize to distant sites, particularly the lungs and bones. Unlike papillary thyroid cancer (PTC), which typically has a favorable prognosis, FTC is associated with a higher risk of distant metastasis and recurrence. The development of the FTC is driven by a complex interplay of genetic mutations, environmental factors, and hormonal influences. Key genetic alterations include mutations in the RAS family genes and the BRAF gene, as well as TERT promoter mutations, all of which contribute to tumor progression and adverse outcomes.
Fig.1 Volcano plots show that the HO-1 expression is upregulated in FTC tissues compared to adjacent tissues. (Jannin A.,
et al., 2022)
Pathogenesis of Follicular Thyroid Cancer (FTC)
The development of follicular thyroid cancer (FTC) is a multifactorial process, intricately influenced by genetic, environmental, and hormonal factors. Genetic mutations, particularly in the RAS family genes, BRAF, and the TERT promoter, are central to the pathogenesis of FTC. These mutations can trigger uncontrolled cell proliferation and drive tumor progression. Environmental factors, such as radiation exposure and iodine deficiency, also significantly contribute to the risk of developing FTC. Additionally, elevated levels of thyroid-stimulating hormone (TSH) can stimulate thyroid cell proliferation, further exacerbating the risk of FTC development.
Diagnostics Development for Follicular Thyroid Cancer (FTC)
Molecular Markers
Molecular markers play a crucial role in the diagnosis and prognosis of follicular thyroid cancer (FTC). The identification of specific genetic alterations, such as BRAF V600E mutations and RAS mutations, helps differentiate FTC from benign thyroid nodules. Additionally, TERT promoter mutations are emerging as significant prognostic indicators, associated with a higher risk of metastasis and recurrence.
MicroRNA (miRNA) Analysis
MicroRNAs (miRNAs) are small non-coding RNA molecules that play a critical role in regulating gene expression. Emerging research has identified specific miRNAs as potential biomarkers for follicular thyroid cancer (FTC), offering valuable assistance in both diagnostic and prognostic evaluations. By profiling miRNA expression, researchers can gain deeper insights into the molecular mechanisms driving FTC development and progression.
Imaging Techniques
Advanced imaging modalities, including ultrasound, CT, and PET, are indispensable in the diagnosis and surveillance of FTC. Ultrasound serves as the initial imaging method for assessing thyroid nodules, providing detailed anatomical information and guiding biopsy procedures. CT and PET scans, on the other hand, are crucial for detecting distant metastases, particularly in high-risk cases. When integrated with molecular markers, these imaging techniques significantly enhance the precision of FTC diagnosis and inform more effective therapeutic planning.
Next-Generation Sequencing (NGS)
Next-generation sequencing (NGS) is a highly effective tool for identifying a broad spectrum of genetic alterations in follicular thyroid cancer (FTC), including mutations, gene fusions, and copy number variations. This comprehensive approach offers a detailed molecular characterization of the tumor, thereby facilitating the development of personalized therapeutic strategies. NGS can detect mutations in key genes such as BRAF, RAS, and TERT, while also uncovering novel genetic alterations that may represent potential therapeutic targets.
Therapeutics Development for Follicular Thyroid Cancer (FTC)
- Targeted Therapies
Targeted therapies focus on specific genetic alterations in FTC. BRAF inhibitors, such as vemurafenib and dabrafenib, are effective in treating BRAF V600E-mutant FTC. MEK inhibitors, when combined with BRAF inhibitors, can enhance therapeutic efficacy. Tyrosine kinase inhibitors (TKIs), including sorafenib and lenvatinib, are approved for the therapeutic of radioactive iodine-refractory FTC. These drugs inhibit multiple tyrosine kinases involved in tumor growth and angiogenesis.
- Immunotherapies
Immunotherapies targeting immune checkpoints, such as PD-1/PD-L1, are being explored in clinical trials for advanced FTC. These therapies aim to boost the immune system's ability to recognize and attack cancer cells. While the efficacy of immunotherapies in FTC is still under investigation, early results show promise in improving outcomes.
Table 1. Molecular alterations in follicular cell-derived thyroid cancer with selected targeted therapeutics. (Capdevila J., et al., 2022)
| Oncogenic driver |
Targeted therapy |
Number of patients with thyroid cancer included in efficacy analysis |
Efficacy in patients with thyroid cancer |
| Response rate |
Median duration of response (months) |
Median OS (months) |
Median PFS (months) |
| NTRK gene fusion |
Larotrectinib |
PTC: 20
FTC: 2
ATC: 7 |
ORR: 71% (2 CR, 18 PR, 4 SD) |
24-month DoR: 81% |
24-month OS: 76% |
24-month PFS: 69% |
| Entrectinib |
TC: 13 (subtype not specified) |
ORR: 53.8% |
13.2 |
NR |
NR |
| RET gene fusion or mutation |
Pralsetinib |
PTC: 9 |
ORR: 89% (89% PR) |
NE |
NR |
NR |
| ALK rearrangement |
Crizotinib |
ATC: 1 |
PR (90% across all pulmonary lesions) |
NE |
NE |
NE |
| TSC2 mutation/MTOR mutation |
Everolimus |
ATC: 1 |
Near CR |
18 |
NR |
NR |
Disclaimer: Protheragen focuses on providing preclinical research services. This table is for information exchange purposes only. This table is not a treatment plan recommendation. For guidance on treatment options, please visit a regular hospital.
Our Services
At Protheragen, we offer a comprehensive suite of diagnostic and therapeutic development services for FTC. Our services range from target development to preclinical studies, leveraging cutting-edge technologies and a multidisciplinary approach to drive innovation in FTC therapeutics.
Disease Models
- TPO-Cre/LSL-K-RasG12D/PTENf/f Model
- TPO-Cre/PRKAR1Af/f/PTENf/f Model
- TPO-Cre/H-RasG12V/PTENf/f Model
- TRβPV/PV Model
Protheragen's preclinical research services focus on elucidating the molecular mechanisms underlying FTC pathogenesis, identifying novel therapeutic targets, and evaluating the efficacy and safety of potential drug candidates. We utilize state-of-the-art in vitro and in vivo models, including patient-derived xenografts (PDXs) and genetically engineered mouse models (GEMMs), to mimic the human disease environment and accelerate the drug discovery process. If you are interested in our services, please feel free to contact us.
References
- Chen, Huanjie, et al. "Curcumin induces ferroptosis in follicular thyroid cancer by upregulating HO-1 expression." Oxidative Medicine and Cellular Longevity 2023.1 (2023): 6896790.
- Wu, Ming-Hsien, et al. "Risk factors and prognosis for metastatic follicular thyroid cancer." Frontiers in endocrinology 13 (2022): 791826.
- Capdevila, Jaume, et al. "Molecular diagnosis and targeted treatment of advanced follicular cell-derived thyroid cancer in the precision medicine era." Cancer Treatment Reviews 106 (2022): 102380.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.
