DeCure for Thyroid Gland Undifferentiated (Anaplastic) Carcinoma
DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for Thyroid Gland Undifferentiated (Anaplastic) Carcinoma — screening already-approved drugs against its 50-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleThyroid Gland Undifferentiated (Anaplastic) Carcinoma maps to a 50-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 thyroid gland undifferentiated (anaplastic) 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
fibroblast growth factor receptor 4 (FGFR4) — FGFR4 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 1~{r}drag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 8KH8 · 1.49 Å · ligand 1-[4-[(1~{R})-1-[3,5-bis(chloranyl)pyridin-4-yl]ethoxy]-5-cyano-pyridin-2-yl]-3-[6-methanoyl-5-[(4-methyl-2-oxidanylidene-piperazin-1-yl)methyl]-3-(2-morpholin-4-ylethoxy)pyridin-2-yl]urea (VVW). Experimental structure, not a prediction.
What the evidence adds up to
Anaplastic thyroid carcinoma is an extremely aggressive solid tumour that resists most therapeutic efforts and is almost always fatal. It typically arises as a terminal dedifferentiation of unrecognised long-standing differentiated thyroid carcinoma. Current chemotherapeutic agents are not capable of consistent beneficial therapeutic responses, although rare patients may gain additional months of survival. Aggressive local tumour control with surgery and external beam radiotherapy may provide palliation and delay eventual death from distant metastatic disease.
Epidemiologic data suggest that many anaplastic thyroid carcinomas arise from transformation of preexisting or coexisting well-differentiated thyroid carcinomas. At the molecular level, the mutations responsible for the anaplastic transformation are incompletely understood, although the mutational events are thought to involve tumour suppressor genes. A study of coexisting well-differentiated and anaplastic tumours using a molecular genotyping panel of tumour suppressor genes found that the majority of cases have a core of conserved mutations in the two morphologically distinct areas and substantial increases in mutation rates in the anaplastic components.
The prognosis has not changed in recent decades and the median survival does not exceed six months. Only few patients with incidental limited anaplastic thyroid carcinoma will be cured. Different therapeutic options have been explored but the results are disappointing. New drugs and new timing for proper treatment are under investigation. In the current medical era, molecular characteristics of the tumours are being increasingly evaluated for their potential role in establishing diagnosis and to guide management, though knowledge of the molecular profiles of anaplastic thyroid carcinoma is still deficient.
What is still missing is a systemic therapy that produces consistent beneficial responses, a clear understanding of the molecular events driving anaplastic transformation, and effective patient stratification to identify the rare patients who might benefit from existing local control measures.
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 · 159 citations
Anaplastic thyroid carcinoma: A therapeutic challenge
AbstractAnaplastic thyroid carcinoma is an extremely aggressive solid tumor that resists most therapeutic efforts and is almost always fatal. It typically arises as a terminal dedifferentiation of unrecognized long-standing differentiated thyroid carcinoma. Current chemotherapeutic agents are not capable of consistent beneficial therapeutic responses, although rare patients may gain additional months of survival. Aggressive local tumor control with surgery and external beam radiotherapy may provide palliation and delay eventual death from distant metastatic disease. This disease challenges clinicians and researchers to develop new systemic therapies as well as to aggressively treat differentiated thyroid cancers before they become anaplastic tumors.
The American Journal of Surgical Pathology · 2003 · 90 citations
Molecular Evidence of Anaplastic Transformation in Coexisting Well-Differentiated and Anaplastic Carcinomas of the Thyroid
AbstractAnaplastic thyroid cancer is a rare but nearly universally fatal tumor. Epidemiologic data suggest that many anaplastic thyroid carcinomas arise from transformation of preexisting or coexisting well-differentiated thyroid carcinomas. At the molecular level, the mutations responsible for the anaplastic transformation are incompletely understood, although the mutational events are thought to involve tumor suppressor genes. To examine transformation from a well-differentiated thyroid carcinoma to anaplastic carcinoma, we studied coexisting well-differentiated (Hürthle cell and papillary carcinoma) and anaplastic tumors with a molecular genotyping panel of tumor suppressor genes associated with thyroid neoplasia. The patterns of allelic loss in our results showed that the majority of cases have a core of conserved mutations in the two morphologically distinct areas and substantial increases in mutation rates in the anaplastic components.
Integrated Therapeutic Strategies for Anaplastic Thyroid Carcinoma
AbstractAnaplastic thyroid carcinoma (ATC) is a very rare neoplasm with an aggressive course. The prognosis has not changed in the last decades and the median survival does not exceed six months. Only few patients with incidental limited ATC will be cured. Different therapeutic options have been explored but the results are disappointing. At present, new drugs and new timing for proper treatment are under investigation. In this short review we have summarized these recent developments.
AbstractAbstract Thyroid neoplasms comprise a heterogeneous group of tumors, arising most commonly from follicular cells. While some neoplasms such as the papillary thyroid carcinoma have been widely studied and reported in the literature, our knowledge of the less common entities, including anaplastic thyroid carcinoma and medullary thyroid carcinoma is still deficient. In the current medical era, molecular characteristics of the tumors are being increasingly evaluated for their potential role in establishing diagnosis and to guide management. In this review article, we discuss some of the less common thyroid neoplastic entities, with a special focus on their molecular profiles. In addition, we share our own institutional experience obtained from molecular profiling of anaplastic thyroid carcinoma and medullary thyroid carcinoma.
IntechOpen eBooks · 2022 · 0 citations · open access
Approach and Management of Anaplastic Carcinoma Thyroid
AbstractAnaplastic carcinoma thyroid, also known as undifferentiated thyroid carcinoma, is a rare but highly aggressive malignant tumor, which accounts for 2–3% of all thyroid malignancies. It is mostly seen in elderly females in their 6th or 7th decade. It carries a very bad prognosis with an average median survival of 5 months. Patients often present with a rapidly growing, painful, woody hard lower anterior neck mass fixed to underlying structures. In addition to local invasion, patients also present with regional nodal spread and distant metastasis. Though the risk factors for anaplastic carcinoma thyroid are unknown, most of them develop in the setting of long-standing goiter, possibly in an undiagnosed, well-differentiated thyroid carcinoma. Management of anaplastic carcinoma thyroid demands a multidisciplinary approach with the involvement of surgeon, radiation oncologist, radiologist, and endocrinologist. The conventional treatment of anaplastic carcinoma thyroid includes surgery, radiation, and chemotherapy. Recently, multitarget tyrosine kinase inhibitors are also incorporated into the treatment. However, prognosis of the disease is very poor with 4 months of overall survival of 35% and overall disease-specific mortality of 98–99%. In this chapter, we discuss how to approach the condition and various treatment strategies to provide improved treatment outcomes for patients diagnosed with anaplastic carcinoma thyroid.
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.
DeCure is a research and publication project, not medical advice and not a treatment. "DeCure for X" describes a research goal, not a claim that a cure exists. Backing a cure is a contribution to fund the research — it is not an investment, and confers no yield, royalty, equity or IP ownership. Papers are published open-access by the DeCure.ai DAO.
