DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for Thymoma — screening already-approved drugs against its 29-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleThymoma maps to a 29-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 thymoma 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
HRas proto-oncogene, GTPase (HRAS) — HRAS 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 gnpdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 8ELT · 1.66 Å · ligand PHOSPHOAMINOPHOSPHONIC ACID-GUANYLATE ESTER (GNP). Experimental structure, not a prediction.
What the evidence adds up to
Invasive thymoma carries a poor 5-year survival despite surgery and radiation. A 1976 report notes that several chemotherapy combinations—cisdiamminedichloroplatinum, prednisone, adriamycin, nitrogen mustard-vincristine-vinblastine-procarbazine, and bleomycin-adriamycin-CCNU-vincristine—produced only short-term remissions, and the authors called for cooperative studies given the small number of cases at any single institution. A 2005 review states that combination chemotherapy in advanced disease yields a 50–80% objective response rate, but these results come from small studies; neoadjuvant chemotherapy or radiotherapy has been used for tumours that are not readily resectable.
Surgery remains the mainstay, and complete resection is the strongest prognostic factor. A 2015 systematic review of 1,061 patients across 14 observational studies compared video-assisted thoracoscopic surgery (VATS) with open thymectomy. Five-year overall survival and 10-year recurrence-free survival were similar or higher with VATS. VATS also showed 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%). Conversion rate from VATS to open was 3.1%, and 30-day mortality was 0% in the VATS group versus 0.3% in the open group. The authors note that adequately powered randomised trials are still needed.
A 2010 study of 63 patients treated between 1966 and 2006 reported 10-year locoregional recurrence-free survival of 79%, disease-free survival of 57%, and overall survival of 57%. Masaoka stage was an independent prognostic factor for all three endpoints; higher photon energies and surgery followed by radiotherapy or chemoradiotherapy also improved survival. Common toxicities included lung fibrosis (36%, mostly asymptomatic), pneumonitis (9%), and oesophagitis (4%). A 2016 review states that after complete resection, recurrence rates range from 5% to 50%, and management of recurrent disease remains controversial, with reoperation preferred but multimodal treatments also used.
A 2022 genetic sequencing study of 27 thymoma samples from Indonesian patients found TP53 exon 6 mutations in 7.4% and EGFR exon 18 mutations in 7.4%; intronic mutations in EGFR exons 19 and 21 were each seen in one sample. The authors conclude that TP53 and EGFR mutations are not frequent in this population and that these genes do not appear central to thymoma pathogenesis, though two samples carried mutations that might warrant further investigation for prognostication or targeted therapy. What remains missing are adequately powered randomised trials comparing surgical approaches, prospective studies to clarify the role of radiotherapy in early-stage disease, and larger genetic or biomarker studies that could identify actionable targets or stratify patients by recurrence risk.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Annals of Internal Medicine · 1998 · 148 citations
A Multidisciplinary Approach to Therapy for Unresectable Malignant Thymoma
AbstractBACKGROUND: The therapeutic outcome for unresectable, locally advanced, malignant thymoma has been poor. OBJECTIVE: To improve tumor resectability and patient survival rates by studying a multimodal approach to therapy for unresectable malignant thymoma. DESIGN: Prospective cohort study. SETTING: Tertiary care cancer center. PARTICIPANTS: All eligible patients had newly diagnosed, histologically proven, unresectable malignant thymoma. INTERVENTION: The treatment regimen consisted of induction chemotherapy (three courses of cyclophosphamide, doxorubicin, cisplatin, and prednisone), surgical resection, postoperative radiation therapy, and consolidation chemotherapy (three courses of cyclophosphamide, doxorubicin, cisplatin, and prednisone). Tissue samples were taken at the time of surgical resection for assessment of tumor necrosis and Ki-67 expression. MEASUREMENTS: Tumor response and resectability (both overall and after induction chemotherapy) and disease-free survival rate in patients who received multimodal therapy. RESULTS: 13 patients were consecutively enrolled from February 1990 to December 1996, and 12 evaluable patients were assessed for response. Disease responded to induction chemotherapy completely in 3 patients (25%) and partially in 8 patients (67%); 1 patient had a minor response (8%). Eleven patients had surgical resection; 1 refused surgery. Tumors were removed completely in 9 (82%) and incompletely in 2 (18%) of 11 patients who had been receiving radiation therapy and consolidation chemotherapy. All 12 patients are alive (100% at 7 years), with a median follow-up of 43 months, and 10 patients are disease free (73% disease-free survival at 7 years). A high correlation was seen between tumor necrosis after induction chemotherapy and Ki-67 expression (r=-0.88). CONCLUSIONS: Aggressive multimodal treatment is highly effective and may cure locally advanced, unresectable malignant thymoma.
AbstractDespite conventional therapy, including surgery and radiation, 5-year survival for invasive thymoma remains poor. Chemotherapeutic agents, including cisdiamminedichloroplatinum, prednisone, adriamycin and nitrogen mustard-vincristine-vinblastine-procarbazine, and bleomycin-adriamycin-CCNU-vincristine have produced short-term remissions. In view of the small number of cases seen in any one institution, a cooperative study to evaluate chemotherapeutic efficacy in malignant thymoma would seem worthwhile.
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.
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.
Journal of Cardiothoracic Surgery · 2016 · 44 citations · open access
The clinical features, diagnosis and management of recurrent thymoma
AbstractThymoma is a disease with malignant potential, which has a recurrence rate after complete resection ranging from 5 to 50 %. Multiple studies on the risk factors, treatment or prognosis have been reported. Many of them are controversial, however. In this review, we summarized some accepted risk factors, means of diagnosis and different treatments of recurrent thymoma. The risk factors of recurrent thymoma haven't been well-studied, and its management remains controversial. We reviewed the literatures and found some key points which should be noticed during the surgery of initial thymoma. Although reoperation should be taken into account preferentially, multimodal treatments are also available. The prognosis are also been discussed.
Asian Pacific Journal of Cancer Prevention · 2022 · 6 citations · open access
TP53 and EGFR Mutational Status in Thymoma: A Genetic Sequencing Study
AbstractBACKGROUND AND OBJECTIVE: Thymoma is a rare malignant tumor that usually with an indolent presentation, which was falsely assumed to be benign previously. The tumor suppressor P53 (TP53) and EGFR gene mutate most frequently in human cancers. We tried to investigate the presence of TP53 and EGFR mutations among thymoma patients referred to an Indonesian referral respiratory hospital and to discuss its potential role in thymoma management and prognosis. MATERIAL AND METHODS: Surgically resected tumor tissues were collected from thymoma patients and then underwent genomic analysis. PCR was performed on the extracted Paraffinized DNA to amplify exon 6 of TP53 and exons 18, 19, and 21 of EGFR. The evaluation of mutational status was done using direct sequencing and sequence analysis of purified PCR products. RESULTS: Among 27 collected samples, TP53 exon 6 mutation, namely missense mutation and nonsense mutation, was observed in two samples (7.4%). EGFR exon 18 mutation, namely E709K and nonsense mutation, was found in 2 samples (7.4%). An intronic mutation in EGFR exon 19 (3.7%) and exon 21 (3.7%) was observed in one sample. CONCLUSION: TP53 and EGFR mutations were not most frequent, so it seems that these genes are not involved in the pathogenesis of thymoma in Indonesian patients. Nevertheless, we found two samples with a significant mutation in p53 and EGFR genes, suggesting further research on thymoma prognostification and targeted therapy.
Reports of Practical Oncology & Radiotherapy · 2010 · 5 citations · open access
Thymoma: Results of treatment and role of radiotherapy
AbstractPURPOSE: The aim of this study is to assess results of treatment, factors influencing prognosis with regard to causes of failure and treatment tolerance in patients with thymoma. MATERIAL AND METHODS: Between 1966 and 2006, 63 patients with thymoma had been treated at the Centre of Oncology in Krakow. Patients were treated by means of different treatment modalities: surgery followed by radiotherapy (52%), radiotherapy alone (13%), chemoradiotherapy alone (15%), surgery followed by chemoradiotherapy (5%), surgery alone (5%) and others. RESULTS: The 10-year locoregional recurrence-free survival (LRRFS) was 79%, disease free survival (DFS) was 57% and overall survival (OS) was 57%. Masaoka stage was the only independent prognostic factor for LRRFS. Masaoka stage and method of radiotherapy delivery (higher photon energies), were independent prognostic factors for OS. For DFS, the independent prognostic factors were age, type of treatment (favoured surgery followed by radiotherapy or chemoradiotherapy), Masaoka stage and year of start of treatment. Most common reactions were lung fibrosis in 36% of patients (mainly asymptomatic in most patients), pneumonitis (9%) and oesophagitis (4%). CONCLUSIONS: Surgery combined with radiotherapy and chemoradiotherapy and modern radiotherapy techniques are correlated with improvement of survival in patients with early stage thymoma.
AbstractThymoma is a potential malignant disease with a recurrence rate of 10% to 30% after complete resection. There is no agreement on the treatment strategy and standard for recurrent thymoma. The treatment methods include reoperation, chemotherapy, radiotherapy, targeted therapy and immunotherapy. In this article, we review the previous literature and summarize the indications, efficacy and prognosis of different treatments for recurrent thymoma, so as to provide some reference for treatment criteria for recurrent thymoma.
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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