DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for thyroid neoplasm — screening already-approved drugs against its 44-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleThyroid neoplasm maps to a 44-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 drugapprovedSelpercatinibTyrosine-protein kinase receptor RET inhibitor · Kinesin-1 heavy chain/ Tyrosine-protein kinase receptor RET inhibitor
Structures already discussed alongside thyroid neoplasm in the retrieved literature, rendered from public PubChem SMILES. Which drugs appear here reflects the evidence found, not a ranked prediction.
Molecular view
Structure of RET protein tyrosine kinase — Selpercatinib has a real, experimentally solved structure in complex with this target (PDB 7JU6, 2.06 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 q6gdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 7JU6 · 2.06 Å · ligand Selpercatinib (Q6G). Experimental structure, not a prediction.
What the evidence adds up to
Vandetanib, an oral inhibitor of VEGFR, EGFR, and RET tyrosine kinases, was tested in a phase 3 randomised placebo-controlled trial for unresectable locally advanced or metastatic medullary thyroid carcinoma. In 231 patients given 300 mg daily versus 100 on placebo, progression-free survival improved (hazard ratio 0.46, 95% CI 0.31–0.69, P < 0.001), but no overall survival difference was seen at publication. Common grade 3/4 adverse effects included diarrhoea, hypertension, QT prolongation, fatigue, and rash; the drug is restricted by a Risk Evaluation and Mitigation Strategy programme because of QT prolongation and sudden death risk. Earlier phase 2 studies had shown antitumour activity in medullary thyroid cancer, though negative results were reported in small cell lung cancer, metastatic breast cancer, and multiple myeloma.
Selpercatinib, a RET kinase inhibitor, has been reported in a 2022 case of a 62-year-old man with ectopic Cushing’s syndrome due to medullary thyroid cancer. After six months, cushingoid features resolved, serum calcitonin fell from 580 pmol/L to 3.5 pmol/L (normal < 3), and at 12 months calcitonin normalised to 1.5 pmol/L with profound tumour volume reduction. Two other similar cases were noted. A 2023 Korean real-world case series described four patients: two with advanced medullary thyroid carcinoma previously treated with vandetanib, one with advanced papillary thyroid cancer without prior systemic therapy, and one with advanced papillary thyroid cancer after lenvatinib. Partial responses were observed in all four, with stable response for 11 months in one patient who had intracranial haemorrhage and swallowing difficulty, and improvement in choroidal metastasis, pain, and panic symptoms in others. The series is small and uncontrolled.
For benign solitary solid cold thyroid nodules, a 1995 randomised controlled trial of 80 patients compared suppressive levothyroxine, low-dose potassium iodide (2 mg every two weeks), and no treatment. After one year, mean nodule volume decreased by 40% with levothyroxine (P < 0.001) and by 23% with potassium iodide (P = 0.053), while untreated nodules slightly increased. A clinically relevant reduction of 50% or more occurred in 9 of 23 on levothyroxine, 5 of 25 on potassium iodide, and none of 22 untreated (P = 0.004). Only nodules of 10 mL or less shrank; those of 5 mL or less shrank most often. Drug withdrawal led to resumed growth within four months.
A 1975 commentary argued for reversion to surgery as the treatment of choice for thyrotoxicosis, citing long-term results and economic factors. A 2007 report described plasmapheresis as a safe bridge to thyroidectomy in two adults with complicated thyrotoxicosis when antithyroid drugs failed or could not be used. What remains missing are randomised trials comparing selpercatinib directly with vandetanib in medullary thyroid cancer, longer overall survival data for both drugs, and prospective studies of selpercatinib in differentiated thyroid carcinoma. For benign nodules, no data exist on long-term maintenance therapy or on patient stratification by nodule size and molecular profile.
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 Oncologist · 2009 · 195 citations · open access
Vandetanib (ZD6474), a Dual Inhibitor of Vascular Endothelial Growth Factor Receptor (VEGFR) and Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinases: Current Status and Future Directions
AbstractVandetanib is a novel, orally available inhibitor of different intracellular signaling pathways involved in tumor growth, progression, and angiogenesis: vascular endothelial growth factor receptor-2, epidermal growth factor receptor, and REarranged during Transfection tyrosine kinase activity. Phase I clinical trials have shown that vandetanib is well tolerated as a single agent at daily doses < or =300 mg. In the phase II setting, negative results were observed with vandetanib in small cell lung cancer, metastatic breast cancer, and multiple myeloma. In contrast, three randomized phase II studies showed that vandetanib prolonged the progression-free survival (PFS) time of patients with non-small cell lung cancer (NSCLC) as a single agent when compared with gefitinib or when added to chemotherapy. Rash, diarrhea, hypertension, fatigue, and asymptomatic QTc prolongation were the most common adverse events. Antitumor activity was also observed in medullary thyroid cancer. Four randomized phase III clinical trials in NSCLC are exploring the efficacy of vandetanib in combination with docetaxel, the Zactima in cOmbination with Docetaxel In non-small cell lung Cancer (ZODIAC) trial, or with pemetrexed, the Zactima Efficacy with Alimta in Lung cancer (ZEAL) trial, or as a single agent, the Zactima Efficacy when Studied versus Tarceva (ZEST) and the Zactima Efficacy trial for NSCLC Patients with History of EGFR-TKI chemo-Resistance (ZEPHYR) trials. Based on a press release by the sponsor of these trials, the PFS time was longer with vandetanib in the ZODIAC and ZEAL trials; the ZEST trial was negative for its primary superiority analysis, but was successful according to a preplanned noninferiority analysis of PFS. Ongoing phase II and III clinical trials will better define the appropriate schedule, the optimal setting of evaluation, and the safety of long-term use of vandetanib.
Annals of Internal Medicine · 1995 · 117 citations
Levothyroxine and Potassium Iodide Are Both Effective in Treating Benign Solitary Solid Cold Nodules of the Thyroid
AbstractOBJECTIVE: To determine the effectiveness of levothyroxine and potassium iodide in treating patients with benign solitary cold thyroid nodules. DESIGN: Randomized controlled study. SETTING: Outpatient clinic at a university hospital. PATIENTS: 80 patients with solitary solid cold thyroid nodules found to be benign at cytologic examination were randomly assigned to no treatment, suppressive levothyroxine (thyroid-stimulating hormone level, < 0.3 mU/L), or low-dose potassium iodide (2 mg every 2 weeks). Seventy patients completed the 1-year study. After 1 year, patients receiving treatment discontinued drug therapy and were re-evaluated 4 months later; patients receiving no treatment were given levothyroxine and were followed for a second year. MEASUREMENTS: Nodule volume was measured by ultrasonography at 4-month intervals by an observer masked to treatment assignment. RESULTS: Mean nodule volume decreased by 40% of the basal volume in the 23 patients receiving levothyroxine (P < 0.001) and by 23% of the basal volume in the 25 patients receiving potassium iodide (P = 0.053). Volume slightly increased in the 22 untreated patients (P = 0.085). A clinically relevant reduction in nodule volume (> or = 50%) was observed in 9 of 23 patients treated with levothyroxine, in 5 of 25 patients treated with potassium iodide, and in none of 22 untreated patients (P = 0.004). Only nodules with a volume of 10 mL or less were reduced; nodules with volumes of 5 mL or less shrank most frequently. Nodule volume did not relevantly increase in treated patients but did increase in 3 of the 22 untreated patients. Drug withdrawal resulted in an increased mean nodule volume (P = 0.004) after 4 months. CONCLUSIONS: Levothyroxine and, to a lesser extent, potassium iodide are effective in arresting the growth or in reducing the volume of benign solitary solid cold thyroid nodules, especially small ones; discontinuation of therapy may result in resumed nodule growth.
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.
AbstractFor 30 years the thyrotoxic patient has been subjected to a plurality of treatments by surgery, radio-iodine and long term anti-thyroid drugs. These therapies have been accepted as complementary to the needs of the individual patient, without regard for long term results or the economic situation as it affects both patient and hospital services. In the context of surgical treatment which is now available, it is suggested that the advantages of operation over other therapies presage a reversion to surgery as the treatment of choice.
Current Oncology · 2022 · 10 citations · open access
Successful Treatment with Selpercatinib for Ectopic Cushing’s Syndrome Due to Medullary Thyroid Cancer
AbstractSelpercatinib, a RET kinase inhibitor, is an effective treatment for patients with medullary thyroid cancer with RET mutations. In this paper, we present the case of a 62-year-old man with ectopic Cushing’s syndrome due to medullary thyroid cancer who received treatment with selpercatinib. Six months later, all the cushingoid features had resolved, and s-calcitonin had decreased from 580 pmol/L to 3.5 pmol/L (normal < 3). After further 6 months, s-calcitonin had normalized (1.5 pmol/L), and radiological evaluation showed a profound tumour volume reduction. We are aware of two other cases where treatment with selpercatinib has also been successful. Thus, selpercatinib may be a promising treatment alternative in patients with ectopic Cushing’s syndrome due to medullary thyroid cancer, especially when other treatment options are ineffective or not tolerated.
Current Oncology · 2023 · 9 citations · open access
Initial Experiences of Selective RET Inhibitor Selpercatinib in Adults with Metastatic Differentiated Thyroid Carcinoma and Medullary Thyroid Carcinoma: Real-World Case Series in Korea
Abstract-altered thyroid cancer. We present four cases of patients with advanced thyroid cancer who were treated with selpercatinib. The first patient was a 63-year-old male with advanced medullary thyroid cancer (MTC) treated with vandetanib. Six months ago, he had an intracranial hemorrhage and swallowing difficulty. He started selpercatinib with percutaneous endoscopic gastrostomy (PEG). For 11 months, a partial response (PR) was observed stably with PEG administration without any more cardiovascular events. The second patient was a 67-year-old female with advanced MTC treated with vandetatib. After selpercatinib treatment, a PR was observed for most metastatic sites, including choroidal metastasis. The third patient was a 32-year-old female with advanced papillary thyroid cancer (PTC) without history of systematic treatment. For six months, a PR was observed at her metastatic site with manageable adverse events. The last patient was a 59-year-old female with advanced PTC treated with lenvatinib. She suffered from a panic disorder and pleural pain due to metastasis during lenvatinib treatment. After selpercatinib treatment, her pain and panic symptoms were improved. Facing varying clinical obstacles of the real world, selpercatinib safely proved remarkable therapeutic efficacy regardless of previous treatment or metastatic site.
Clinical Medicine Insights Oncology · 2012 · 5 citations · open access
Efficacy and Tolerability of Pharmacotherapy Options for the Treatment of Medullary Thyroid Cancer
AbstractMetastatic and unresectable medullary thyroid carcinoma (MTC) is often difficult to treat as it is relatively unresponsive to radiation and conventional chemotherapy. This emphasizes the importance of the development of targeted therapies for advanced MTC. Vandetanib was approved by the US Food and Drug Administration for the treatment of symptomatic or progressive MTC in patients with advanced disease in April 2011. This therapy proved to be a breakthrough in the management of MTC. We review the efficacy and safety of this novel treatment and other treatments that are being evaluated in this disease.
E-LEARNING: riesgos y oportunidades de la formación ubicua
AbstractThe standard treatment of complicated thyrotoxicosis and thyroid storm with the concomitant use of antithyroid medication, iodine, beta-blockers, and corticosteroids is successful in most cases. However, treatment options are limited when antithyroidal drugs cannot be used or in cases that are refractory to standard treatment. Plasmapheresis provides a safe and effective strategy when initial treatment fails, facilitating the transition to definitive treatments such as thyroidectomy. We present two adults with complicated thyrotoxicosis successfully treated with plasmapheresis as a bridge therapy to thyroidectomy or as an alternative to drug-induced toxicity.
Disease module: DeepOracle (Open Targets). Approved indication: ChEMBL drug_indication (max_phase=4). Structures: RDKit from PubChem SMILES. Literature: retrieved by DeepSearch across 234,678,978 indexed works, resolved on OpenAlex.
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