Medullary Thyroid Cancer (MTC) is a rare yet highly aggressive thyroid malignancy that arises from the parafollicular C cells within the thyroid gland. Protheragen specializes in providing state-of-the-art diagnostic and therapeutic development services for MTC, harnessing advanced technologies and deep expertise in oncology research to offer comprehensive solutions for this challenging disease.
Overview of Medullary Thyroid Cancer (MTC)
Medullary Thyroid Cancer (MTC) is a rare neuroendocrine malignancy that originates from the parafollicular C cells of the thyroid gland. These C cells, derived from the neural crest, are responsible for producing calcitonin, a hormone that plays a crucial role in calcium homeostasis. MTC can manifest as either sporadic or hereditary, with the hereditary form commonly associated with multiple endocrine neoplasia (MEN) syndromes, specifically types 2 and 3. Although MTC is uncommon, it disproportionately contributes to thyroid cancer-related mortality, underscoring the critical need for early detection and effective therapeutic strategies.
Fig.1 Genotype-phenotype correlations, allelic frequency, and risk levels for medullary thyroid carcinoma behavior. (Gild M. L.,
et al., 2023)
Pathogenesis of Medullary Thyroid Cancer (MTC)
The primary driver of Medullary Thyroid Cancer (MTC) is mutations in the RET (rearranged during transfection) proto-oncogene. The RET gene encodes a receptor tyrosine kinase that regulates critical cellular processes, including differentiation, proliferation, and apoptosis. Mutations in the RET gene result in its constitutive activation, which in turn triggers uncontrolled cell growth and tumor development. These mutations can be either germline (inherited) or somatic (acquired). Germline mutations are linked to hereditary MTC and multiple endocrine neoplasia (MEN) syndromes, while somatic mutations are typically found in sporadic MTC cases. Common RET mutations occur in codons 609, 611, 618, 620, 634, and 918. Additionally, mutations in the RAS gene are occasionally seen in sporadic MTC, though these tend to be less aggressive compared to RET-driven tumors.
Diagnostics Development for Medullary Thyroid Cancer (MTC)
Serum Calcitonin
Calcitonin serves as a highly sensitive tumor marker for Medullary Thyroid Cancer (MTC). Elevated calcitonin levels in the blood can signal the presence of MTC, even before symptoms appear. Preoperative measurement of serum calcitonin enhances diagnostic accuracy and aids in surgical planning.
Fine-Needle Aspiration (FNA) Biopsy
FNA biopsy is used to obtain tissue samples from thyroid nodules for cytological evaluation. While it helps diagnose MTC, its sensitivity is limited, and false-negative results can occur. Measuring calcitonin in FNA washout fluids (FNA-Ctn) can significantly improve diagnostic accuracy.
Genetic Testing
Analysis of germline and somatic RET mutations is crucial for diagnosing hereditary and sporadic MTC, respectively. If a germline RET mutation is identified, genetic counseling and testing of first-degree relatives are strongly recommended.
Carcinoembryonic Antigen (CEA)
CEA is another marker used in combination with calcitonin. Elevated CEA levels may indicate metastatic disease and are valuable for monitoring therapeutic response.
Therapeutics Development for Medullary Thyroid Cancer (MTC)
- Multikinase Inhibitors (MKIs)
Vandetanib and Cabozantinib: These MKIs target multiple tyrosine kinases, including RET, VEGF receptors, and EGFR, and have shown efficacy in prolonging progression-free survival in advanced MTC cases. However, their use is limited by toxicity and the development of drug resistance.
- Highly Selective RET Inhibitors
Selpercatinib and Pralsetinib: These next-generation RET inhibitors offer higher selectivity for RET, resulting in improved tolerability and efficacy compared to MKIs. Clinical trials have demonstrated significant response rates and prolonged progression-free survival in RET-mutated MTC cases.
Table 1. Outcomes of kinase inhibitors FDA approved for MTC. (Gild M. L., et al., 2023)
| Kinase inhibitor |
Outcome |
Stage |
| Vandetinib |
Median PFS 30.5 months, HR: 0.46 (0.31-0.69), OS HR: 0.89 (0.48-1.65) |
Phase III |
| Cabozantinib |
Median PFS 11.2 months, HR: 0.28 (0.19-0.40), median OS 44.3 months, HR: 0.85 (0.64-1.12) |
Phase III |
| Selpercatinib |
Pretreated patients ORR of 69% (95% CI 55-81%) and 1-year PFS of 82% (95% CI 69-90%)
Treatment-naive patients: ORR 73% (95% CI 62-82%) and 1-year PFS 64% (95% CI 37-92%). |
Phase I/II |
| Praseltinib |
Treatment naive ORR 71% (95% CI 48-89%), pretreated patients ORR 60% (95% CI 46-73%) |
Phase I/II |
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
Protheragen provides comprehensive services for the diagnosis and development of therapies for medullary thyroid cancer (MTC). Our expertise spans from early research to preclinical development, utilizing cutting-edge technologies and approaches to address the unique challenges presented by MTC. Our services include state-of-the-art genetic testing and development of targeted therapies, ensuring our clients receive the highest quality support to meet their MTC R&D needs.
Disease Models
- Genetically engineered mouse models carrying RET mutations
- CGRP-v-Ha-ras mouse model
- Mouse models with mutations in cell-cycle control genes
- MTC xenograft murine model
- Drosophila cancer model
- Chick chorioallantoic membrane (CAM)
Protheragen's preclinical research services for MTC include in vitro and in vivo models of MTC, pharmacokinetic and pharmacodynamic studies, and toxicology assessments. We utilize state-of-the-art facilities and methodologies to accelerate the discovery and development of novel MTC therapeutics. If you are interested in our services, please feel free to contact us.
References
- Gild, Matti L., et al. "Medullary thyroid cancer: updates and challenges." Endocrine Reviews 44.5 (2023): 934-946.
- Kaliszewski, Krzysztof, et al. "Update on the diagnosis and management of medullary thyroid cancer: what has changed in recent years?." Cancers 14.15 (2022): 3643.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.
