DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for follicular thyroid carcinoma — screening already-approved drugs against its 48-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleFollicular thyroid carcinoma maps to a 48-gene Open Targets module — the target space DeCure's AI scientist screens approved drugs against.
DeCure.ai methodSignature reversal (LINCS) plus network proximity (STRING) rank already-approved drugs likely to perturb this module — the same engine that produces DeCure.ai's repurposing hypotheses.
Repurposing thesisScreening approved medicines against this disease module, then publishing the evidence for the strongest candidate. Known pharmacology and human exposure data make the first question sharper — they do not establish safety or efficacy in a new indication.
Research record
01
ResearchComing soon
Candidate research + dossier — target rationale, drug-repurposing thesis and evidence pack.proof: Published dossier + on-chain hash
02
ValidationComing soon
In-vitro biological validation at a contract research org (CRO).proof: CRO contract + in-vitro report
03
Peer review & paperComing soon
Peer-reviewed paper published open-access (preprint + journal).proof: DOI + open-access link + on-chain hash
Current lead
No approved-drug candidate for follicular thyroid carcinoma is corroborated in the literature DeepSearch retrieved. Some conditions are managed with non-pharmacological care — a device, surgery or physical therapy — rather than a medicine; that may be the case here, or the literature we found may simply be too sparse yet to support a drug-repurposing angle.
Molecular view
protein kinase cAMP-dependent type I regulatory subunit alpha (PRKAR1A) — PRKAR1A is one of the genes genetically linked to this disease in Open Targets — shown as context, not as a drug target we're pursuing: no approved-drug candidate for this disease is yet corroborated in the literature we found.
Loading structure…
helix sheet pcgdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 5KJZ · 1.347 Å · ligand CYCLIC GUANOSINE MONOPHOSPHATE (PCG). Experimental structure, not a prediction.
What the evidence adds up to
In a series of 65 patients with pure follicular thyroid carcinoma treated between 1956 and 1990, mean follow-up was 10.4 years. Three patients (5%) died of thyroid cancer, and two were living with distant metastatic disease at last follow-up. Median tumour size was 2.2 cm. Fine-needle aspiration biopsy in 20 patients showed a follicular neoplasm in 18 (90%). Pre-operative TSH-suppressive thyroid hormone therapy for an average of 4.5 months in 19 patients led to no change in tumour size in 10 (53%), an increase in 5 (26%), and a decrease in 2 (11%). Intraoperative frozen section correctly diagnosed cancer in only 3 of 39 patients (8%). Permanent surgical complications occurred during 3 of 96 operations.
A separate cohort of 1039 consecutive thyroid carcinoma cases followed for an average of 11.9 years included 102 encapsulated well-differentiated follicular-patterned tumours diagnosed as carcinoma by complete capsular invasion or papillary carcinoma-type nuclei. None of these 102 cases were among the 67 patients from the cohort who died of thyroid carcinoma. The authors concluded that such tumours do not play a significant role in thyroid carcinoma fatality rates.
In one reported case, a man with metastatic follicular carcinoma developed thyrotoxicosis after total thyroidectomy, which was controlled with antithyroid drugs. Radioactive iodine treatment reduced the size of distant metastases and diminished thyroid hormone production. The abstract states that radioactive iodine yields a remission rate as high as 33% in follicular carcinoma complicated by hyperthyroidism. Another case report describes a 13.5 cm follicular thyroid carcinoma with lung, humerus, and T9 spine metastases that carried concurrent NRAS Q61K and GNAS R201H mutations and showed a good response to radioactive iodine.
A 2020 review notes that early-stage follicular thyroid carcinoma is managed with total thyroidectomy followed by radioactive iodine ablation and external beam radiation. For advanced, radioactive-iodine-refractory cases, targeted therapy with tyrosine kinase inhibitors is described as an essential therapeutic option, but the review does not provide specific response rates or survival data from clinical trials comparing different TKIs in follicular carcinoma specifically. What remains missing are prospective trials that stratify patients by mutational profile (such as NRAS or GNAS status) and that compare tyrosine kinase inhibitors head-to-head in radioactive-iodine-refractory follicular carcinoma, as well as funding for such studies.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Cancer · 1993 · 146 citations
Diagnosis, treatment, and outcome of follicular thyroid carcinoma
AbstractBackground. There have been numerous studies concerning the diagnosis, treatment, and prognosis of patients with papillary thyroid carcinoma, but relatively few addressing patients with follicular carcinoma. Methods. The authors analyzed their experience with 65 patients who underwent 96 thyroid operations for pure follicular thyroid carcinoma from 1956 to 1990. Results. The patients were 43 women and 22 men with a mean age of 45 years who were followed postoperatively for a mean of 10.4 years. Fifty-two patients (80%) were seen initially with a solitary thyroid nodule, and 24 (37%) had symptoms at presentation. Median tumor size was 2.2 cm. Fine-needle aspiration biopsy was performed in 20 patients, revealing a follicular neoplasm in 18 patients (90%) and an inadequate specimen in 2 patients. Nineteen patients received thyroid-stimulating hormone (TSH)-suppressive thyroid hormone therapy for an average of 4.5 months before surgery; tumor size remained the same in 10 patients (53%), increased in 5 (26%), and decreased in 2 (11%). At presentation, six patients had lymph node involvement, three had locally invasive tumors, and two had distant metastases. Initial operative treatment was lobectomy in 32 patients (49%), total thyroidectomy in 15 patients (23%), lobectomy plus contralateral partial or subtotal lobectomy in 11 patients (17%), and lesser procedures in 7 patients (11%). Twenty-nine patients had a completion total thyroidectomy, so that final surgical treatment consisted of total thyroidectomy in 44 patients (68%). Among 39 patients having intraoperative frozen section, only 3(8%) were correctly diagnosed as having cancer. Permanent complications occurred during 3 of the 96 operations. Three patients (5%) have died of thyroid cancer (one with anaplastic transformation) since thyroidectomy, and two are living with distant metastatic disease. Conclusions. Patients with follicular thyroid cancer, when first examined, usually have solitary thyroid nodules that are follicular neoplasms by aspiration cytology, and these nodules fail to regress in response to TSH-suppressive therapy. Frozen section rarely aids in management. The preferred treatment for follicular neoplasms is lobectomy followed by completion total thyroidectomy for histologically proven carcinomas larger than 1.0 cm. Total thyroidectomy allows use of thyroglobulin and radioiodine scanning to detect and treat metastatic disease. Complications of thyroidectomy were uncommon, and the mortality rate in treated patients was relatively low.
The American Journal of Surgical Pathology · 2010 · 143 citations
Encapsulated Well-differentiated Follicular-patterned Thyroid Carcinomas Do Not Play a Significant Role in the Fatality Rates From Thyroid Carcinoma
AbstractA cohort of 1039 consecutive cases of thyroid carcinoma treated at a single institution and followed for an average of 11.9 years or until death included 102 encapsulated well-differentiated follicular-patterned tumors that had been diagnosed as carcinoma because of complete capsular invasion and/or papillary carcinoma-type nuclei. None of these cases were among the 67 patients from the cohort who died as a result of their thyroid carcinoma. The results of this study and a critical review of the pertinent literature indicate that tumors with these features are associated with an extremely favorable outcome and that they do not play a significant role in the fatality rate of thyroid carcinoma.
Vandetanib for the Treatment of Medullary Thyroid Carcinoma
AbstractOBJECTIVE: To review the place in therapy of vandetanib for medullary thyroid carcinoma (MTC). DATA SOURCES: Literature searches were performed in Ovid MEDLINE, EMBASE, and Google Scholar using the search terms ZD6474 OR vandetanib OR Caprelsa combined with medullary thyroid carcinoma. STUDY SELECTION AND DATA EXTRACTION: Two phase 2 trials and 1 phase 3 trial were identified. DATA SYNTHESIS: Vandetanib is approved for the treatment of unresectable, locally advanced or metastatic MTC in patients with symptomatic or progressive disease. In the phase 3 randomized, double-blind, placebo-controlled trial, vandetanib 300 mg daily (n = 231) was compared with placebo (n = 100). Vandetanib-treated patients experienced a significant improvement in progression-free survival (PFS; hazard ratio [HR] = 0.46; 95% CI = 0.31-0.69; P < .001). No difference in overall survival (OS) was seen at the time of publication. Most adverse effects were grade 1 or 2 and managed by dose interruptions or reductions. The most common grade 3/4 adverse effects were diarrhea, hypertension, QT prolongation, fatigue, and rash. Because of the potential for QT prolongation, torsades de pointes, and sudden death, vandetanib is restricted via a Risk Evaluations and Mitigation Strategy program. CONCLUSIONS: Vandetanib prolongs PFS but has not been shown to improve OS. Vandetanib can be considered for patients with unresectable locoregional disease. It is a first-line option for patients with unresectable symptomatic distant metastases as well as an option for advanced disseminated symptomatic metastatic disease. Vandetanib is expected to be an important addition to the formulary of health plans that provide prescription drug benefits.
Thyrotoxicosis Associated With Distant Metastatic Follicular Carcinoma of the Thyroid
AbstractIn a man with metastatic follicular carcinoma of the thyroid, thyrotoxicosis developed after total thyroidectomy and was successfully treated with antithyroid medications. Treatment with radioactive iodine decreased the size of the distant metastasis and eventually diminished thyroid hormone production. Follicular carcinoma complicated by hyperthyroidism requires vigorous control of the hypermetabolic state. Treatment with radioactive iodine can effectively reduce metabolic complications and tumor bulk, and yields a remission rate as high as 33%.
Indian Journal of Endocrinology and Metabolism · 2018 · 12 citations · open access
Molecular profiling of follicular variant of papillary thyroid cancer reveals low-risk noninvasive follicular thyroid neoplasm with papillary-like nuclear features: A paradigm shift to reduce aggressive treatment of indolent tumors
AbstractINTRODUCTION: Encapsulated follicular variant of papillary thyroid carcinoma (EFVPTC) has been reclassified into noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) and invasive EFVPTC. NIFTP is considered a low-risk neoplasm. Therefore, follicular variant of papillary thyroid cancer (FVPTC) presently has two distinct histopathological subtypes - invasive EFVPTC and infiltrative/diffuse FVPTC. Molecular characteristics of these groups remain unclear. METHODOLOGY: Thirty FVPTCs (10 NIFTPs, 12 invasive EFVPTCs, and 8 infiltrative/diffuse variants) were reviewed and screened for BRAF and RAS mutations by restriction fragment length morphism-polymerase chain reaction (PCR) and Sanger sequencing. The mRNA expression levels of iodine-metabolizing genes were analyzed using real-time PCR. The mutations status and mRNA expression levels were correlated with clinicopathological features. RESULTS: All 10 NIFTPs had predominant follicular pattern. One case showed NRAS mutation, whereas none showed BRAF mutation. All invasive EFVPTC had capsular and/or lymphovascular invasion and 4/12 showed lymph node metastasis. BRAF and NRAS were seen in three cases each of invasive FVPTC. All eight infiltrating/diffuse FVPTCs showed infiltration into adjacent thyroid parenchyma and lymph node metastasis. CONCLUSION: BRAF mutation was observed in 62.5% of cases; however, no NRAS mutation was found. Sodium iodide symporter (NIS) expressions in NIFTP were similar to that of normal thyroid tissue, whereas it was downregulated in invasive and infiltrative/diffuse FVPTC. Our study supports the argument that NIFTP can be considered as low-risk follicular thyroid neoplasm. Those tumors that harbor BRAF mutations may be offered a complete thyroidectomy because they show decreased expression of NIS gene which confers a tendency to lose radioactive iodine avidity and further recurrence of the tumor.
Endocrinology Diabetes and Metabolism Case Reports · 2016 · 11 citations · open access
Follicular thyroid carcinoma with NRAS Q61K and GNAS R201H mutations that had a good 131I treatment response
AbstractUNLABELLED: We report a case of follicular thyroid carcinoma with concomitant NRAS p.Q61K and GNAS p.R201H mutations, which manifested as a 13.5 cm thyroid mass with lung, humerus and T9 spine metastases, and exhibited good response to radioactive iodine treatment. LEARNING POINTS: GNAS p.R201H somatic mutation is an activating or gain-of-function mutation resulting in constitutively activated Gs-alpha protein and downstream cAMP cascade, independent of TSH signaling, causing autonomously functioning thyroid nodules. NRAS p.Q61K mutations with GNAS p.R201H mutations are known for a good radioactive iodine treatment response.Further exploration of the GNAS-activating pathway may provide therapeutic insights into the treatment of metastatic follicular carcinoma.
Journal of Neurology Research Review & Reports · 2020 · 0 citations · open access
Targeted Therapy in Management of Advanced Follicular Thyroid Carcinoma
AbstractFollicular thyroid carcinoma (FTC) is the second most common malignancy involving the thyroid glands. Early stages of FTC are managed with total thyroidectomy followed by 131I ablation and external beam radiation therapy. Targeted therapy with tyrosine kinase inhibitors (TKIs) is an essential therapeutic option for the management of advanced cases of radioactive iodine refractory. This review will investigate the clinical data for the therapeutic use of targeted therapy in advanced FTC and compare the efficacy of different targeted therapy used in managing the patients.
Disease module: DeepOracle (Open Targets). Structures: RDKit from PubChem SMILES. Literature: retrieved by DeepSearch across 234,678,978 indexed works (targeted per-candidate search), resolved on OpenAlex.
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