DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for Thymoma Type B3 — screening already-approved drugs against its 17-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleThymoma Type B3 maps to a 17-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
approvedSorafenibApproved drug
Structures already discussed alongside thymoma type b3 in the retrieved literature, rendered from public PubChem SMILES. Which drugs appear here reflects the evidence found, not a ranked prediction.
Molecular view
Human P38 MAP kinase — Sorafenib has a real, experimentally solved structure in complex with this target (PDB 3GCS, 2.1 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 baxdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 3GCS · 2.1 Å · ligand Sorafenib (BAX). Experimental structure, not a prediction.
What the evidence adds up to
A systematic review of 1,061 patients across 14 studies found that video-assisted thoracoscopic surgery (VATS) for thymoma resection produced five-year overall survival and ten-year recurrence-free survival similar to or higher than open thymectomy. The VATS group had reduced mean intraoperative blood loss (131.8 vs. 340.5 mL), shorter mean hospital stays (7.0 vs. 9.8 days), and lower rates of postoperative pneumonia (1.9% vs. 4.1%). Conversion from VATS to open surgery occurred in 3.1% of cases, and 30-day mortality was 0% in the VATS group versus 0.3% in the open group.
Thymomas have a low mutational burden. The most frequent recurrent mutation is a missense change in GTF2I, p.(Leu404His), which is specific to thymic epithelial tumours. The indolent types A and AB express the C19MC miRNA cluster, which is silenced in the more aggressive type B thymomas and thymic carcinomas. Thymic carcinomas show a higher mutational burden with frequent TP53 mutations, epigenetic regulatory gene mutations, and CDKN2A loss. A microarray analysis of 31 thymomas identified six driving genes (FANCI, CAPD3, NCGAP, OXCT1, EPHA1, MCM2) with significantly abnormal expression, and copy-number variation affected genes including upregulation of E2F2, EphA1, CCL25, and MCM2, and downregulation of IL-6, CD36, FABP4, SH2D1A, and MYOC. KEGG analysis showed altered expression in ten signalling pathways, including cell cycle and p53 pathways.
For advanced or recurrent thymic epithelial tumours, a multimodality approach including radiation and chemotherapy is used because no effective treatment exists for metastatic or refractory disease. Targeted agents have been investigated in prospective clinical trials with varying success. Two cases of thymoma achieved striking responses to sorafenib in combination with lapatinib, but these are anecdotal reports.
What is still missing are adequately powered randomised trials comparing VATS to open surgery, a clearer understanding of which genomic alterations are actionable, and prospective trials that stratify patients by histological subtype or molecular profile rather than treating all thymomas as a single disease.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
PubMed · 2015 · 72 citations
Video-assisted thoracoscopic surgery versus open thymectomy for thymoma: a systematic review.
AbstractBACKGROUND: Video-assisted thoracoscopic surgery (VATS) thymectomy is an increasingly utilized alternative to traditional open approaches for the resection of thymomas. Recent studies have suggested comparable survival and oncological efficacy as well as reduced perioperative morbidity when using the VATS approach. This current systematic review thus aimed to critically evaluate existing evidence for the efficacy and safety of VATS versus open (transsternal or transthoracic) thymectomy for thymomas. METHODS: Six electronic databases were searched from their date of inception to April 2015. Relevant studies were identified using specific eligibility criteria and data were extracted and analyzed based on predefined primary and secondary endpoints. RESULTS: Fourteen comparative observational studies with a total of 1,061 patients were obtained for qualitative assessment, data extraction and analysis. Five-year overall survival and 10-year recurrence-free survival was similar or higher in patients undergoing VATS compared to open thymectomy. On average, the VATS group also demonstrated reduced intraoperative blood loss (131.8 vs. 340.5 mL), shorter hospital stays (7.0 vs. 9.8 days), and lower rates of postoperative pneumonia (1.9% vs. 4.1%). The mean rate of conversion from VATS to open thymectomy was relatively low (3.1%), while 30-day mortality remained low in both the VATS and open groups (0 vs. 0.3%). CONCLUSIONS: The current evidence suggests that VATS thymectomy for thymoma has at least equal if not superior oncological efficacy and survival outcomes, as well as reduced perioperative complications, compared to open surgery. Further adequately powered studies and future randomized trials are required to confirm these findings.
Journal of Thoracic Disease · 2020 · 18 citations · open access
Genomic alterations in thymoma—molecular pathogenesis?
AbstractThymomas and thymic carcinomas (TCs) are neoplasms of thymic epithelial cells. Thymomas exhibit a low mutational burden and a few recurrently mutated genes. The most frequent missense mutation p.(Leu404His) affects the general transcription factor IIi (GTF2I) and is specific for thymic epithelial tumors (TETs). The clinically indolent types A and AB thymomas express the miRNA cluster C19MC. This miRNA cluster known to be the largest in the human genome, is-with expression otherwise restricted mostly to embryonal tissue-silenced in the more aggressive type B thymomas and TCs. Thymomas associated with the autoimmune disease myasthenia gravis (MG) exhibit more frequent gene copy number changes and an increased expression of proteins homologous to molecules that are targets for autoantibodies. TCs, however, display a higher mutational burden, with frequent mutations of TP53 and epigenetic regulatory genes and loss of CDKN2A. The knowledge of molecular alterations in TETs fosters the understanding of their pathogenesis and provides guidance for further studies that may lead to the development of targeted therapies.
Targeted Therapy for Thymic Epithelial Tumors: A New Horizon? Review of the Literature and Two Cases Reports
AbstractSurgical resection remains the cornerstone of therapy for early-stage thymic epithelial tumors (TETs), while in advanced or recurrent forms, a multimodality approach incorporating radiation and chemotherapy is required. Given the absence of effective treatment options for metastatic/refractory TETs and the poor related prognosis, there is a compelling need to identify promising 'drugable' molecular targets. Initial reports of activity from targeted agents in TETs derived from anecdotal cases have been often associated with specific activating mutations. Only in recent years, several agents have been formally investigated into prospective clinical trials, with varying success rates. We reviewed the literature on targeted therapy in TETs along with two cases of thymoma achieving striking responses to sorafenib in combination with lapatinib.
[Analysis of Gene Variation in Thymoma by Microarray].
AbstractBACKGROUND: Thymoma is the most common malignant tumor in anterior mediastinum, and its specific pathogenesis is still unclear. This limits the study of targeted drugs for thymoma. The aim of the study is to investigate the genes and signal pathways of thymoma, and provide help for the research of thymic tumor pathogenesis using the technology of second-generation genechip to analyze thymoma. METHODS: From January 2015 to December 2017, we analyzed 31 cases of thymoma by CapitaBio mRNA expression profile genechip technology, and then confirmed the genes by reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: We found some genes with different expression levels between thymoma and surrounding thymus tissue. Among them, six driving genes (FANCI, CAPD3, NCAPG, OXCT1, EPHA1 and MCM2) were significantly abnormal in thymoma. Some specific genes affected by copy-number variation were detected: E2F2, EphA1, CCL25 and MCM2 were significantly up-regulated, while IL-6, CD36, FABP4, SH2D1A and MYOC genes were significantly down-regulated. KEGG database analysis showed that the expression of 10 signaling pathway genes was generally up-regulated or down-regulated, such as systemic lupus erythematosus, viral oncogenes, primary immunodeficiency, cell cycle genes and p53 signaling pathway, which may be related to occurrence of thymoma. CONCLUSIONS: We found a variety of genes abnormally expressed in thymoma, which will provide reference for the study of pathogenesis and biomarkers of thymoma in the future.
Oxford University Press eBooks · 2016 · 0 citations
Neoplasms of the thymus
AbstractThymic tumours are among the malignant diseases with very low incidence. Therefore clinical research and development of new treatment options pose an ongoing challenge. For treatment of thymomas the following methods are used: surgery, radiotherapy, chemotherapy, and targeted drugs. The optimal type and sequence of therapy depends on tumour stage, histological subtype, and general health condition of the patient. A complete surgical resection is still the mainstay of therapy. For patients with incomplete resection or in locally advanced stages adjuvant radio/chemotherapy is recommended. Neoadjuvant treatment approaches and novel targeted therapies are under investigation. Lifelong follow-up has to be preferred because of possible late recurrences.
A late relapse thymoma and pure red cell aplasia case with an over 5 years of clinical response under everolimus
AbstractAlthough several agents showed some clinical activity in patients with recurrent thymoma, there is no standard treatment option. Here, we report a late relapse thymoma and pure red cell aplasia case, responsive to everolimus with over 5 years of clinical benefit following multiple lines of treatment. Everolimus controlled the rapidly progressive disease in our patient without significant toxicity.
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.
