DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for thyroid cancer — 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 moduleThyroid cancer 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 thyroid cancer 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
Differentiated thyroid cancer accounts for most thyroid cancers in the United States, and a significant minority of patients do not respond to conventional surgery, radioiodine, or levothyroxine. For progressive, radioiodine-nonresponsive disease, high-dose Adriamycin therapy provides a 30% to 40% partial response rate, but long-term cures are rare. Combination chemotherapy has not shown greater benefit than Adriamycin alone and carries greater toxicity. Retinoic acid, octreotide, and tamoxifen were being studied as future possibilities in 1999.
A 2017 population-based cohort study of 2444 patients with differentiated thyroid cancer ≤4 cm in Ontario, Canada, compared outcomes across geographic regions with different treatment philosophies. Treatment varied significantly across the province, but when regions with more extensive treatment were compared to those with less extensive therapy, 15-year survival, recurrence, and survival after recurrence were similar. The authors concluded that these findings support the trend toward more conservative management.
Mouse models have validated the importance of the cAMP/protein kinase A and MAPK signalling pathways in papillary thyroid cancer, and RAS mutations play a role in both papillary and follicular thyroid cancer development. Mice with overactivation of the PI3K-AKT and/or thyrotropin-regulated pathways develop follicular thyroid cancer. A 2024 editorial notes that thyroid cancer ranges from indolent papillary to aggressive and lethal anaplastic types, and that new molecular players have been identified using animal models, human samples, and proteomic analysis.
A 2024 meta-analysis of targeted drugs for radioiodine-refractory differentiated thyroid cancer reports significant therapeutic effects from these drugs and supports a strategy to balance them against adverse effects. The meta-analysis also identifies some new drugs that show potential superior benefits. What remains missing is prospective evidence that any molecular stratification reliably selects patients who will benefit from these targeted agents, and the high cost and toxicity of long-term therapy are not resolved by the meta-analysis.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Seminars in Surgical Oncology · 1999 · 143 citations
Management of the patient with progressive radioiodine non-responsive disease
AbstractDifferentiated thyroid cancer accounts for a majority of the nearly 200,000 people in the United States with thyroid cancer. A significant minority of patients with thyroid cancer do not respond to conventional therapy (surgery, radioiodine, levothyroxine [LT4]). Current therapy for progressive, radioiodine non-responsive differentiated thyroid cancer includes surgery and external-beam irradiation (with or without low-dose weekly Adriamycin) for neck disease, and high-dose Adriamycin therapy for widely metastatic disease. Adriamycin therapy provides a 30% to 40% partial response of disease, but long-term cures are rare. Studies of combination chemotherapy do not show greater benefit than therapy with Adriamycin alone and carry understandably greater toxicity. Retinoic acid, octreotide, and tamoxifen therapies are currently being studied as future therapeutic possibilities. Chemotherapy may prove useful not only as a tumoricidal agent but as therapy for tumor re-differentiation in preparation for radioiodine therapy.
AbstractBACKGROUND: Thyroid cancer is the most common endocrine tumor and is increasing in incidence. The aim of this study was to review mouse models of differentiated thyroid cancer and how they elucidate human thyroid cancer biology. SUMMARY: Differentiated thyroid cancer, primarily papillary and follicular, comprises the majority of thyroid cancers. There has been tremendous growth in the cross-talk between basic science and clinical practice for thyroid cancer management. Insight into the framework of genes responsible for differentiated thyroid cancer has been gained through the use of mouse models. Common genetic alterations found in human papillary thyroid cancer such as RET/PTC rearrangements or the BRAF(V600E) mutation have genetically modified mouse counterparts. These and other preclinical mouse models have validated the importance of the cyclic adenosine monophosphate (cAMP)/protein kinase A and mitogen-activated protein kinase (MAPK) signaling pathways in papillary thyroid cancer (PTC). RAS mutations have a role in both papillary and follicular thyroid cancer development. Mice with overactivation of the phosphatidylinol-3-kinase (PI3K)-AKT and/or thyrotropin-regulated signaling pathways have been found to develop follicular thyroid cancer. Additional mouse models of thyroid cancer that utilize inducible expression systems are in development or are being characterized and will better reflect the majority of human thyroid cancers which are non-hereditary. Advances in in vivo imaging of mice allow for earlier detection of metastasis and the ability to follow tumor growth or regression which may be used in evaluation of pharmaceutical agents. CONCLUSIONS: Mouse models have expanded our understanding of the altered signaling pathways that contribute to thyroid cancer tumorigenesis and provide a powerful tool to develop novel diagnostic approaches and therapies.
Journal of the National Comprehensive Cancer Network · 2013 · 12 citations · open access
New Developments in Thyroid Cancer
AbstractThyroid cancer is common but rarely deadly. Unfortunately, when the disease becomes refractory to radioactive iodine (RAI), few effective treatment options remain. This situation is changing, however, with the availability of multitargeted tyrosine kinase inhibitors. Cabozantanib and vandetanib, both recently FDA-approved for advanced or metastatic disease, have more than doubled progression-free survival in medullary thyroid cancer. New agents in the pipeline may yield even better outcomes, as discussed by Dr. Robert I. Haddad at the NCCN 18th Annual Conference.
Do Lower-Risk Thyroid Cancer Patients Who Live in Regions with More Aggressive Treatments Have Better Outcomes?
AbstractBACKGROUND: The management of differentiated thyroid cancer has traditionally consisted of total thyroidectomy with or without adjuvant radioactive iodine. However, in the last two decades, this approach has been challenged, with the consideration of more conservative approaches such as less radical surgery and deferring adjuvant treatment, especially in lower-risk patients. The objective of this study was to consider the effectiveness of current treatment options by comparing the survival outcomes from different geographic regions with different treatment philosophies. This study design was based on the concept of natural experiments in patient care that occur when physicians in different regions treat the spectrum of typical patients with varying treatments. METHOD: This population-based retrospective cohort study investigated 2444 patients with differentiated thyroid cancer ≤4 cm between 1990 and 2001 from Ontario, Canada. Extent of disease and extent of surgery were abstracted from pathology reports and were linked to downstream administrative medical information on treatments and outcomes. Patient demographics, tumor characteristics, treatments, and outcomes were compared between those geographic regions with more aggressive treatments and those regions with less aggressive treatments. RESULTS: Treatment varied across the province. When comparing outcomes in regions where patients had more extensive treatment to those in regions where patients had less extensive therapy, similar rates were found for 15-year survival, recurrence, and survival after recurrence. CONCLUSION: There were significant variations in treatment but no differences in outcomes for regions with more versus less aggressive approaches. These findings support the trend toward more conservative management approaches in the treatment of thyroid cancer.
The Surgical Approach to Differentiated Thyroid Cancer
AbstractThe incidence of thyroid cancer is increasing rapidly. A large percentage of new cases identified fall into a low-risk category. As the incidence has increased, clinical experience has confirmed that the majority of patients will have excellent outcomes and that those at risk of doing badly can be reliably identified. Treatment for thyroid cancer is predominantly surgical. The decision about how aggressively this disease should be managed has remained controversial due to the excellent outcomes irrespective of the nature of surgical procedure chosen. This article reviews the developments in our understanding of the biology of thyroid cancer and the evidence that supports the approach to management.
Frontiers in Endocrinology · 2024 · 1 citations · open access
Editorial: New molecular pathways in thyroid cancer and pathophysiology: role of coding and noncoding genes
AbstractThyroid cancer is the most common endocrine malignancy arising from different cell types that compose thyroid gland, namely, follicular cells and C-cells or parafollicular cells. Within the follicular cell-derived thyroid cancer, several variants can be identified that exhibit heterogeneous behavior ranging from indolent papillary thyroid cancer (PTC) to very aggressive and lethal anaplastic thyroid cancer (ATC), turning thyroid cancer into a fruitful field for investigation of tumor biology. In this context, the Research Topic "New molecular pathways in thyroid cancer and pathophysiology: Role of coding and noncoding genes" compiled several articles that provided novel aspects of thyroid cancer biology, adding new layers to the complexity of the disease.Regarding the oncogenesis aspect, new molecular players have been identified using animal models, human samples and proteomic analysis. Overall, we hope that these 11 articles published in the Research Topic "New molecular pathways in thyroid cancer and pathophysiology: Role of coding and noncoding genes" have shed new light on the understanding of thyroid biology and pathogenesis, while provided new insights into this molecular field that is emerging from the interpretation of data generated in the omics era.
Efficacy and safety of targeted therapy for radioiodine-refractory differentiated thyroid cancer: a meta-analysis
AbstractIn this study we performed a meta-analysis on the currently used targeting drugs for radioiodine-refractory differentiated thyroid cancer (RR-DTC) based on an extensive literature review. This should be the largest meta-analysis of this type with most extensive and comprehensive analyses of various aspects of the therapeutic effects and adverse effects of the drugs in RR-DTC. The results demonstrate the significant therapeutic effects of these drugs and support a measured strategy to balance them against the adverse effects of the drugs. This study also identifies some new drugs that show potential superior benefits in the treatment of RR-DTC, with strong promises for future progress of the field.The results of this study are presented in the manuscript. Other results, including Detailed search strategy, Egger's test results and sensitivity analysis, are included in the supplymentary appendix.
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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