DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for differentiated thyroid carcinoma — screening already-approved drugs against its 45-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleDifferentiated thyroid carcinoma maps to a 45-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
approvedVandetanibApproved drug
Structures already discussed alongside differentiated thyroid carcinoma in the retrieved literature, rendered from public PubChem SMILES. Which drugs appear here reflects the evidence found, not a ranked prediction.
Molecular view
Crystal structure of phosphorylated RET tyrosine kinase domain — Vandetanib has a real, experimentally solved structure in complex with this target (PDB 2IVU, 2.5 Å). This is the drug's own deposited structure, not a prediction, and confirms it is a structurally characterised molecule rather than an untested guess.
Loading structure…
helix sheet zd6drag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 2IVU · 2.5 Å · ligand Vandetanib (ZD6). Experimental structure, not a prediction.
What the evidence adds up to
In a prospective multi-institutional registry of 4941 patients with differentiated thyroid carcinoma followed for a median of 6 years, overall survival improved in stage III patients who received postoperative radioiodine (risk ratio 0.66, p=0.04) and in stage IV patients who received both total or near-total thyroidectomy and radioiodine (risk ratios 0.66 and 0.70, combined p=0.049). Moderate thyroid hormone suppression therapy, maintaining TSH in the subnormal-normal range, was associated with significantly improved overall survival across all stages (risk ratios from 0.13 in stage I to 0.33 in stage IV) and improved disease-free survival in stages I through III (risk ratios 0.52, 0.40, 0.18). No additional survival benefit was seen with more aggressive suppression that kept TSH undetectable or subnormal, even in patients who developed distant metastatic disease during follow-up. Lower initial stage and moderate suppression were independent predictors of improved overall survival in the first three years after diagnosis.
Vandetanib, an oral tyrosine kinase inhibitor blocking RET, VEGFR-2, VEGFR-3, and EGFR, has been studied in advanced medullary thyroid carcinoma and in dedifferentiated papillary thyroid cancer that no longer responds to radioiodine. Its main reported effect in aggressive medullary thyroid cancer is prolongation of progression-free survival and disease stabilisation. Significant side effects include fatigue, hypertension, QTc prolongation, cutaneous rash, hand-and-foot syndrome, and diarrhoea; severe side effects can require stopping the drug. The review notes that long-term efficacy may be limited by drug resistance, and that effectiveness might be improved by molecular characterisation of tumours and by testing sensitivity of individual patient's thyroid cancer cells to different tyrosine kinase inhibitors. Combination studies with other agents such as irinotecan and bortezomib are under evaluation.
A separate review of tyrosine kinase inhibitors in differentiated thyroid carcinoma states that metastatic disease that has become inoperable or refractory to radioactive iodine is associated with poor survival, and that results of conventional treatments in that setting have been disappointing. Newer strategies for radioiodine-refractory thyroid cancer include redifferentiation drugs and molecular targeted drugs, both of which may induce tumour cells to regain iodine avidity, allowing combined radioiodine therapy that might exploit a synergistic effect. The review notes that such combined therapy is expected to improve therapeutic effects and prognoses, but does not provide survival or response data from completed trials.
What remains missing are large randomised trials with long follow-up that compare these targeted agents head-to-head against placebo or standard care in radioiodine-refractory differentiated thyroid carcinoma, as well as prospective data on which molecular subtypes benefit most. The cost of such trials and the difficulty of stratifying patients by tumour genetics and prior treatment history are unresolved barriers.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
The Journal of Clinical Endocrinology & Metabolism · 2015 · 185 citations · open access
Long-Term Outcomes Following Therapy in Differentiated Thyroid Carcinoma: NTCTCS Registry Analysis 1987–2012
AbstractCONTEXT: Initial treatments for patients with differentiated thyroid cancer are supported primarily by single-institution, retrospective studies, with limited follow-up and low event rates. We report updated analyses of long-term outcomes after treatment in patients with differentiated thyroid cancer. OBJECTIVE: The objective was to examine effects of initial therapies on outcomes. DESIGN/SETTING: This was a prospective multi-institutional registry. PATIENTS: A total of 4941 patients, median follow-up, 6 years, participated. INTERVENTION: Interventions included total/near-total thyroidectomy (T/NTT), postoperative radioiodine (RAI), and thyroid hormone suppression therapy (THST). MAIN OUTCOME MEASURE: Main outcome measures were overall survival (OS) and disease-free survival using product limit and proportional hazards analyses. RESULTS: Improved OS was noted in NTCTCS stage III patients who received RAI (risk ratio [RR], 0.66; P = .04) and stage IV patients who received both T/NTT and RAI (RR, 0.66 and 0.70; combined P = .049). In all stages, moderate THST (TSH maintained subnormal-normal) was associated with significantly improved OS (RR stages I-IV: 0.13, 0.09, 0.13, 0.33) and disease-free survival (RR stages I-III: 0.52, 0.40, 0.18); no additional survival benefit was achieved with more aggressive THST (TSH maintained undetectable-subnormal). This remained true, even when distant metastatic disease was diagnosed during follow-up. Lower initial stage and moderate THST were independent predictors of improved OS during follow-up years 1-3. CONCLUSIONS: We confirm previous findings that T/NTT followed by RAI is associated with benefit in high-risk patients, but not in low-risk patients. In contrast with earlier reports, moderate THST is associated with better outcomes across all stages, and aggressive THST may not be warranted even in patients diagnosed with distant metastatic disease during follow-up. Moderate THST continued at least 3 years after diagnosis may be indicated in high-risk patients.
Drug Design Development and Therapy · 2015 · 36 citations · open access
Selective use of vandetanib in the treatment of thyroid cancer
AbstractVandetanib is a once-daily orally available tyrosine kinase inhibitor that works by blocking RET (REarranged during Transfection), vascular endothelial growth factor receptor (VEGFR-2, VEGFR-3), and epidermal growth factor receptor and to a lesser extent VEGFR-1, which are important targets in thyroid cancer (TC). It is emerging as a potentially effective option in the treatment of advanced medullary thyroid cancer (MTC) and in dedifferentiated papillary thyroid cancer not responsive to radioiodine. The most important effect of vandetanib in aggressive MTC is a prolongation of progression-free survival and a stabilization of the disease. Significant side effects have been observed with the vandetanib therapy (as fatigue, hypertension, QTc prolongation, cutaneous rash, hand-and-foot syndrome, diarrhea, etc), and severe side effects can require the suspension of the drug. Several studies are currently under way to evaluate the long-term efficacy and tolerability of vandetanib in MTC and in dedifferentiated papillary TC. The efficacy of vandetanib in patients with MTC in long-term treatments could be overcome by the resistance to the drug. However, the effectiveness of the treatment could be ameliorated by the molecular characterization of the tumor and by the possibility to test the sensitivity of primary TC cells from each subject to different tyrosine kinase inhibitor. Association studies are evaluating the effect of the association of vandetanib with other antineoplastic agents (such as irinotecan, bortezomib, etc). Further research is needed to determine the ideal therapy to obtain the best response in terms of survival and quality of life.
Tyrosine kinase inhibitors in differentiated thyroid carcinoma: a review of the clinical evidence
AbstractDifferentiated thyroid carcinoma (DTC) is a highly prevalent endocrine malignancy. The majority of DTCs are slowly progressive and, when identified at an early stage, frequently cured with adequate surgical management and radioactive iodine-131 ablation therapy. Metastatic DTC that has become inoperable or refractory to radioactive iodine-131, however, is associated with a poor survival. Results of conventional treatment modalities have been disappointing and, therefore, new therapies are needed. As a result of the increasing knowledge of the biologic basis for thyroid cancer, therapeutic agents that target involved biologic abnormalities have been identified. Multiple clinical trials have been initiated and performed in the past years. In this article conventional and new treatment modalities in differentiated advanced thyroid cancer are described, with the focus on kinase inhibitors.
Journal of Korean Thyroid Association · 2015 · 2 citations · open access
New Strategies for Combined Radioiodine Therapy in Refractory Thyroid Cancer
AbstractThe prognosis of differentiated thyroid cancer (DTC) is excellent, which is mainly due to the high therapeutic efficacy of radioactive iodine (RAI) therapy as well as indolent nature of thyroid cancer itself. Although most patients with DTC are well treated with RAI therapy, a certain number of patients have been suffered from refractoriness to RAI therapy. To overcome refractoriness, many alternative treatments have been investigated, and they could be classified based on the mechanisms of action; redifferentiation drug and molecular targeted drug. Not only redifferentiated drugs but also molecular targeted drugs could induce differentiation of thyroid cancer cells. Consequently, alternative treatments allowing tumor cells of RAI avidity followed by RAI therapy could utilize a synergistic effect of both therapies. Combined RAI therapy is expected to improve therapeutic effects and prognoses of RAI refractory thyroid cancers.
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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