Papillary Thyroid Cancer (PTC) is the most common endocrine malignancy, originating from the follicular cells of the thyroid gland. At Protheragen, we specialize in providing comprehensive preclinical research and development services specifically designed to address the unique challenges of PTC. Our expertise covers the entire drug development pipeline, encompassing target discovery and validation through to preclinical testing.
Overview of Papillary Thyroid Cancer (PTC)
Papillary thyroid cancer (PTC) is the most common type of thyroid malignancy, comprising nearly 80% of all thyroid cancer cases. Typically characterized by a well-differentiated cellular structure and a relatively slow clinical progression, PTC can, in some cases, evolve into more aggressive variants such as poorly differentiated thyroid cancer (PDTC) or anaplastic thyroid cancer (ATC). Over the past few decades, the incidence of PTC has increased significantly, primarily due to advancements in diagnostic technologies that enable the detection of small, non-palpable thyroid nodules. Although PTC generally has a favorable prognosis, it can recur and metastasize, highlighting the need for robust diagnostic and therapeutic approaches.
Fig.1 Pattern of recurrence of papillary thyroid carcinoma (PTC). (Gild M. L.,
et al., 2023)
Pathogenesis of Papillary Thyroid Cancer (PTC)
The pathogenesis of PTC is complex and multifactorial, involving a combination of genetic mutations and environmental influences. Well-established risk factors for PTC include exposure to ionizing radiation, a family history of thyroid cancer, chronic lymphocytic thyroiditis, iodine deficiency, and female gender. At the molecular level, PTC is characterized by the presence of driver mutations in over 98% of cases. These mutations commonly involve the mitogen-activated protein kinase (MAPK) signaling pathway, such as activating mutations in the BRAF and RAS genes. Additionally, fusions involving the RET and NTRK1 genes are frequently observed. The progression from well-differentiated thyroid cancer (DTC) to more aggressive forms, such as poorly differentiated thyroid cancer (PDTC) or anaplastic thyroid cancer (ATC), is often driven by further genetic alterations, including mutations in the p53 and TERT genes.
Diagnostics Development for Papillary Thyroid Cancer (PTC)
Fine-Needle Aspiration (FNA) Cytology
Fine-needle aspiration (FNA) cytology continues to be the cornerstone for evaluating thyroid nodules. This procedure involves using a fine needle to extract cells from the nodule, which are then examined microscopically. FNA cytology is highly effective, with a sensitivity of 65% to 98%, specificity of 72% to 100%, and overall accuracy of 84% to 95%. However, it can sometimes produce indeterminate results, which may lead to unnecessary surgical interventions.
Molecular Diagnostics
Molecular diagnostics have revolutionized the evaluation of thyroid nodules. The ThyroSeq v3 genomic classifier, for example, analyzes over 12,000 mutation hotspots and 120 fusion types, offering a robust predictive value for malignancy. Additionally, the gene-expression classifier (GEC) identifies benign nodules by examining the expression of 167 specific genes. These molecular tests significantly enhance the diagnostic accuracy of FNA, thereby reducing the number of unnecessary thyroidectomies.
Imaging Techniques
Ultrasound (US) is the primary imaging modality for thyroid nodule evaluation, capable of detecting nodule characteristics associated with malignancy. Advanced techniques such as contrast-enhanced ultrasound (CEUS) and ultrasound elastography (USE) have further improved the accuracy of US in differentiating between malignant and benign nodules. These enhanced imaging methods provide crucial information to support clinical decision-making.
Therapeutics Development for Papillary Thyroid Cancer (PTC)
- Thyroid Hormone Replacement Therapy
Thyroid hormone replacement therapy is a key strategy for suppressing thyroid-stimulating hormone (TSH) levels, thereby reducing the risk of disease recurrence. This approach is particularly advantageous for high-risk patients, as it helps to inhibit the growth and spread of residual cancer cells.
- Targeted Therapy
Tyrosine kinase inhibitors (TKIs) have emerged as important therapeutics for aggressive and radioiodine-resistant papillary thyroid carcinoma (PTC). Approved TKIs, such as Lenvatinib, Vandetanib, Sorafenib, and Cabozantinib, target specific molecular pathways involved in cancer progression. These targeted therapies offer new and effective options for patients with advanced disease.
- Immunotherapy
Recent research indicates that immunotherapy, particularly immune checkpoint inhibitors, holds promise for the therapeutic of advanced PTC. This approach is especially relevant for the BRAF-like B subtype identified in recent studies. By enhancing the body's immune response against cancer cells, immunotherapy provides a potentially transformative therapeutic option for patients who do not respond to conventional therapies.
Table 1. Molecular alterations in 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% |
| RET gene fusion or mutation |
Pralsetinib |
PTC: 9 |
ORR: 89% (89% PR) |
NE |
NR |
NR |
| BRAF V600E mutation |
Dabrafenib and RAI |
PTC: 10 |
PR: 2
SD: 4 |
NR |
NR |
NR |
| BRAF V600E mutation |
Dabrafenib and trametinib |
PTC: 27 (24 assessable) |
ORR: 54% |
13.3 |
NR |
15.1 |
| BRAF V600E mutation |
Vemurafenib |
PTC: 51
Treatment naive: 26
Previous VEGFR: 25 |
Treatment naive ORR: 39% (10 PR), Previous VEGFR ORR: 27% (6 PR) |
Treatment naive: 16.5
Previous VEGFR: 7.4 |
Treatment naive: NR
Previous VEGFR: 14.4 |
Treatment naive: 18.2
Previous VEGFR: 8.9 |
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 a comprehensive suite of services dedicated to the development of diagnostics and therapeutics for papillary thyroid cancer (PTC). Our offerings span the entire research and development continuum, covering molecular diagnostics, targeted therapies, and immunotherapy. By harnessing state-of-the-art technologies and deep expertise, we deliver innovative solutions for the detection and therapeutics of PTC.
Disease Models
- TPO-Cre/LSL-Braf Models
- TG-CreER T2 /Braf CA Models
- TPO-CreER T2 /Braf CA Models
- TG-RET-PTC1/Trp53− / −Models
- TG-RET-PTC3/Trp53− / −Models
Protheragen's preclinical research services for PTC are designed to accelerate the development of effective diagnostics and therapeutics. Our services include molecular profiling, biomarker discovery, and preclinical testing of novel compounds. We utilize state-of-the-art techniques to identify genetic mutations and biomarkers that can guide targeted therapy, ensuring that our clients have access to the latest advancements in PTC research. If you are interested in our services, please feel free to contact us.
References
- de Carvalho, Andre Ywata, et al. "Predictive factors for recurrence of papillary thyroid carcinoma: analysis of 4,085 patients." Acta otorhinolaryngologica italica 41.3 (2021): 236.
- 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.
