DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for Thymoma Type B1 — screening already-approved drugs against its 2-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 B1 maps to a 2-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
approvedSunitinibApproved drug
Structures already discussed alongside thymoma type b1 in the retrieved literature, rendered from public PubChem SMILES. Which drugs appear here reflects the evidence found, not a ranked prediction.
Molecular view
KIT kinase domain — Sunitinib has a real, experimentally solved structure in complex with this target (PDB 3G0E, 1.6 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 b49drag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 3G0E · 1.6 Å · ligand Sunitinib (B49). Experimental structure, not a prediction.
What the evidence adds up to
In a 27-year surgical series of 217 myasthenia gravis patients who underwent thymectomy, 62 (28.4%) had thymoma. After a mean follow-up of 119 months, 71% of all patients improved clinically (25% asymptomatic without medication, 46% improved with reduced medication), 18% were stable, 5% deteriorated, and 6% died from myasthenia (mean survival 34.3 months). The presence of a thymoma negatively influenced prognosis. Operative mortality was 0.92%. Younger patients and those with shorter symptom duration before surgery had more favourable outcomes.
A 2005 review states that surgery is the mainstay treatment for thymic malignancies and complete resection is the best prognostic factor. Postoperative radiotherapy is controversial in early-stage thymomas. Combination chemotherapy in advanced disease produced a 50–80% objective response rate in small studies. Neoadjuvant chemotherapy or radiotherapy have been used for tumours not readily resectable. The review notes that thymic carcinomas are more aggressive and less common than thymomas.
Deep sequencing of thymomas has failed to identify known oncogenic driver mutations except GTF2I, which occurs predominantly in type A and AB thymomas. A 2020 microarray analysis of 31 thymomas found six driving genes (FANCI, CAPD3, NCAPG, OXCT1, EPHA1, MCM2) significantly abnormal in thymoma, and copy-number variation affecting E2F2, EphA1, CCL25, MCM2 (up-regulated) and IL-6, CD36, FABP4, SH2D1A, MYOC (down-regulated). KEGG analysis showed altered expression in cell cycle, p53 signalling, and other pathways. A 2023 study reports increased TEMRA cells in type B thymoma and suggests IL-8 level in those cells may be a biomarker for hormonotherapy in type B1 and B2 patients. Another 2023 case report describes a 35-year-old man with type B2 thymoma who had R0 resection in 2020, locoregional recurrence in July 2022, resistance to six cycles of chemotherapy, and then started the tyrosine kinase inhibitor sunitinib.
What is still missing: prospective trials that stratify thymoma by subtype (B1, B2, B3) and by molecular markers such as IL-8 or the identified gene expression changes; funding for multi-centre studies large enough to test targeted agents like sunitinib in chemotherapy-resistant B2 thymoma; and a validated biomarker to select patients for hormonotherapy in B1 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.
European Journal of Cardio-Thoracic Surgery · 1999 · 103 citations · open access
Thymectomy for myasthenia gravis: a 27-year experience1
AbstractOBJECTIVE: Thymectomy is considered an effective therapeutic option for patients with myasthenia gravis (MG). We reviewed our 27-year experience with surgical treatment of MG with respect to long-term results and factors affecting outcome. METHODS: Between 1970 and 1997, we performed 232 thymectomies for MG. Fifteen patients were lost to follow-up; the remaining 217 form the object of our study. Sixty-two patients (28.4%) had thymoma. Myasthenia was graded according to a modified Osserman classification: 51 patients (23.5%) were in class I, 81(37.3%) in class IIA, 52 (24%) in class IIB, 26 (12%) in class III and seven (3.2%) in class IV. Mean duration of symptoms before the operation was 12+/-10 months. Fifty-eight thymectomies for thymoma were performed through a median sternotomy and four through a clamshell incision. Forty-six thymectomies for non-thymomatous MG were performed through a standard cervicotomy, 101 procedures through a partial upper sternal-splitting incision and eight through a complete median sternotomy. RESULTS: Operative mortality was 0.92% (two patients). After a mean follow-up of 119 months, 71% of all patients improved their clinical status (25% without medications and asymptomatic; 46% with a reduction of medications and/or clinically improved); 39 (18%) have a stable disease with no clinical modifications; 12 (5%) presented a deterioration of their clinical status with worse symptoms, required more medications, or both. Thirteen patients (6%) died because of MG (mean survival 34.3+/-3.6 months). The presence of a thymoma negatively influenced the prognosis. Younger patients showed a more favorable outcome as well as patients with a shorter duration of symptoms before the operation; patients with lower classes of myasthenia showed a higher rate of remission. CONCLUSIONS: Thymectomy is effective in the management of patients with MG at all stages with low morbidity. Patients with thymoma present a less favorable outcome.
AbstractPURPOSE OF REVIEW: The present review reports findings in the field of epithelial tumors originating from the thymus from the past year and discusses these findings in the context of the literature. RECENT FINDINGS: Epithelial tumors of the thymus are relatively common tumors of the anterior superior mediastinum. Thymomas are usually slowly growing tumors, and their prognosis depends on the macroscopic and microscopic invasion of surrounding tissues. Thymic carcinomas are more aggressive and less common tumors than thymomas and have been increasing in frequency in recent years. Surgery is the mainstay treatment of thymic malignancies, and complete resection represents the best prognostic factor in this disease. Postoperative radiotherapy may be indicated in tumors with invasion of surrounding tissues, but it is controversial in early-stage thymomas. Combination chemotherapy has been employed in several small studies and in advanced disease has been demonstrated to produce a 50-80% objective response rate. Neoadjuvant chemotherapy or external beam radiotherapy have been used with success in patients with tumors that are not readily resectable. Novel antiproliferative systemic agents are being investigated, based on a better understanding of the biology of these tumors. SUMMARY: A better understanding of the clinical behavior of thymomas versus thymic carcinomas and systemic therapies targeted to biologically validated targets in these diseases will help improve efficacy of treatment.
Frontiers in Oncology · 2022 · 17 citations · open access
A phase II study of buparlisib in relapsed or refractory thymomas
AbstractPurpose: To investigate the efficacy and safety of buparlisib, an oral pan-PI3K inhibitor, in relapsed or refractory thymomas. Methods: This was a single center, single arm, open label phase II trial of buparlisib in patients with recurrent thymoma who have progressed after at least one prior line of treatment. The primary endpoint was objective response rate (complete response [CR] + partial response [PR]). Secondary endpoints included toxicity; progression free survival (PFS); overall survival (OS); disease control rate (DCR), i.e., the percentage of patients who achieve either PR or CR or stable disease [SD] for at least 4 months. Results: Between 10/13/2014 and 1/18/2017, 14 patients with stage IV disease were enrolled. Median age was 58y (23-74). 71% were females and 71% white. All patients had WHO B2 (29%) or B3 (71%) thymoma. Patients received buparlisib for a median of 4.5m (2-33). At a median follow up of 16.6m (2.4-31.3), onr patients (7%) achieved a PR. DCR was 50%. Median PFS was 11.1m (95% CI 2.9 - 18.8). Median OS, updated as of March, 2021 was 22.5m (10.7-31.3). Most common grade 3-4 adverse events related to buparlisib were dyspnea (21%), rash (14%), elevated transaminases (14%), cough (7%), pneumonitis (7%), anxiety (7%), fatigue (7%) and hyperglycemia (7%). Reasons for treatment discontinuation included progression of disease (n= 5), rash (n=4), pulmonary toxicity (n=3), sinusitis (n=1), and disseminated toxoplasmosis plus autoimmune cholangitis (n=1). As of 3/2021, 8 patients have died, 7 due to disease progression and 1 due to central nervous system toxoplasmosis and autoimmune cholangitis. Conclusion: Buparlisib showed modest activity in patients with relapsed or refractory thymomas. Further investigation of PI3K pathway targeted therapy in thymoma is warranted. (clinicaltrials.gov ID: NCT02220855). Clinical trial registration: clinicaltrials.gov, identifier (NCT02220855).
Non-Mutational Key Features in the Biology of Thymomas
AbstractThymomas (THs) are a unique group of heterogeneous tumors of the thymic epithelium. In particular, the subtypes B2 and B3 tend to be aggressive and metastatic. Radical tumor resection remains the only curative option for localized tumors, while more advanced THs require multimodal treatment. Deep sequencing analyses have failed to identify known oncogenic driver mutations in TH, with the notable exception of the GTF2I mutation, which occurs predominantly in type A and AB THs. However, there are multiple alternative non-mutational mechanisms (e.g., perturbed thymic developmental programs, metabolism, non-coding RNA networks) that control cellular behavior and tumorigenesis through the deregulation of critical molecular pathways. Here, we attempted to show how the results of studies investigating such alternative mechanisms could be integrated into a current model of TH biology. This model could be used to focus ongoing research and therapeutic strategies.
[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.
Research Square · 2023 · 0 citations · open access
The level of IL-8 in TMERA cells as a biomarker for hormonotherapy in thymoma
AbstractAbstract Thymoma is the most common type of neoplasm in the anterior mediastinum. However, it can be challenging to differentiate thymoma from other anterior mediastinum tumors in this region through imaging examinations. Therefore, the identification of a reliable, unique characteristic for the further study of thymoma is crucial. Our study confirms an increase in TEMRA cells in type B thymoma and suggests that the level of IL-8 in TEMRA cells may be a biomarker indicating hormonotherapy can be an effective treatment for patients with type B1 and B2 thymoma patients.
International Journal of Biomedicine · 2023 · 0 citations · open access
A Rare Case Resistant Chemotherapy Thymoma B2 Type, New Approach
AbstractInvasive thymomas and thymic carcinomas are relatively rare tumors, which together represent about 0.2% to 1.5% of all malignancies.The majority of thymomas (90%) are found in the anterosuperior mediastinum.Type B2 thymoma, one of the rarest cases, was diagnosed in a 35-year-old male.Anamnesis, imaging examination, serological and invasive procedures confirmed the diagnosis.In 2020, the patient was operated on with thymoma R0-resection.The patient showed no progression until July 2022, when a locoregional recurrence was detected.The patient received 6 cycles of chemotherapy, to which the tumor showed resistance.After 6 months, the patient started a treatment with tyrosine kinase inhibitor sunitinib.If a patient is diagnosed with thymoma B2 that does not respond to standard chemotherapy, the tumor can be accepted as an aggressive one requiring a change to a new treatment.
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.
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.
