DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for Thymoma Type AB — screening already-approved drugs against its 13-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 AB maps to a 13-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
approvedLapatinibApproved drugapprovedDasatinibApproved drug
Structures already discussed alongside thymoma type ab 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 EphA4 kinase domain — Dasatinib has a real, experimentally solved structure in complex with this target (PDB 2Y6O, 1.543 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 1n1drag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 2Y6O · 1.543 Å · ligand Dasatinib (1N1). Experimental structure, not a prediction.
What the evidence adds up to
For thymoma type AB, surgery remains the mainstay of treatment. A systematic review of 1,061 patients from 14 studies found that video-assisted thoracoscopic surgery (VATS) produced five-year overall survival and ten-year recurrence-free survival similar to or higher than open thymectomy, with 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 conversion rate from VATS to open surgery was 3.1%, and 30-day mortality was 0% in the VATS group versus 0.3% in the open group. However, a retrospective case series of 19 patients who developed local recurrence after minimally invasive surgery found that all had pleural recurrence on the same side as the surgical approach, and ten also had mediastinal recurrence. The median time to recurrence was 31 months, with relapses seen as late as 130 months. Fifteen of these patients had initially undergone R0 resection, and the median tumour size was 6.2 cm.
For advanced or unresectable disease, chemotherapy has been used. A 2005 review reported that combination chemotherapy in advanced thymoma produced objective response rates of 50–80% in several small studies. A 20-year retrospective study of 29 patients with locally advanced thymoma (Masaoka stage III–IVb) who received preoperative chemotherapy or chemoradiotherapy followed by surgery reported a partial response in 11 patients and stable disease in 18. Complete resection was achieved in 83% of cases. Five-year overall survival was 100% and ten-year overall survival was 87%, but five- and ten-year disease-free survival were both 50%. There were no perioperative deaths, though 21% of patients developed postoperative complications. A 1976 paper noted that various chemotherapeutic regimens, including cisplatin, prednisone, adriamycin, and combinations such as nitrogen mustard-vincristine-vinblastine-procarbazine and bleomycin-adriamycin-CCNU-vincristine, had produced only short-term remissions in invasive thymoma.
Targeted therapies remain experimental. A 2015 review noted that initial reports of activity from targeted agents in thymic epithelial tumours derived from anecdotal cases, often associated with specific activating mutations, and that prospective trials had shown varying success rates. The same review described two cases of thymoma achieving striking responses to sorafenib in combination with lapatinib, but no controlled data for type AB specifically exist.
What is still missing are adequately powered randomised trials comparing surgical approaches, prospective studies of preoperative chemotherapy specifically for type AB thymoma, and validated biomarkers to guide patient selection for targeted agents. The rarity of the disease means that cooperative, multi-institutional efforts are needed to generate reliable evidence.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Cancer · 1976 · 74 citations · open access
Chemotherapy of invasive 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.
Interactive Cardiovascular and Thoracic Surgery · 2018 · 26 citations · open access
Long-term outcomes of advanced thymoma in patients undergoing preoperative chemotherapy or chemoradiotherapy followed by surgery: a 20-year experience
AbstractOBJECTIVES: The results of preoperative chemotherapy or chemoradiotherapy followed by surgery for locally advanced thymoma were analysed. METHODS: Between 1997 and 2016, 29 patients with a thymoma underwent preoperative chemotherapy or chemoradiotherapy followed by surgery. These cases were retrospectively reviewed. RESULTS: The study population included 9 men and 20 women, with a mean age of 48.8 years (range 31-68 years). The preoperative Masaoka stage was III in 12, IVa in 13 and IVb in 4 patients, whereas histological type was B3 in 11, B2 in 9 and others in 5 patients. The mean tumour size was 8.0 ± 2.5 cm (3.4-15.0 cm). The site of infiltration shown in preoperative radiological examinations was the aorta in 6 patients, the superior vena cava in 14 patients and the pulmonary artery trunk in 3 patients, with pleural dissemination detected in 14. Three patients underwent chemoradiotherapy. Chemotherapy regimens given were cisplatin + doxorubicin + vincristine + cyclophosphamide in 9 patients, carboplatin + paclitaxel in 6 patients, cisplatin + doxorubicin + methylprednisolone in 5 patients and others in 9 patients, with partial response obtained in 11 patients and stable disease noted in 18 patients. Complete resection was achieved in 24 (83%) cases. There were no perioperative mortalities, whereas 6 (21%) patients developed postoperative complications. The 5- and 10-year overall survival rates were 100% and 87%, respectively, and 5- and 10-year disease-free survival rates were 50% and 50%, respectively. CONCLUSIONS: Preoperative chemotherapy or chemoradiotherapy followed by surgery for locally advanced thymoma can be performed with an acceptable degree of surgical risk. Such a strategy should be proactively considered, as it can lead to favourable long-term results.
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).
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.
AB018. Local recurrence of thymoma following minimally invasive resection: a retrospective case series
AbstractBackground: Surgery remains the mainstay treatment for non-metastatic thymic epithelial tumors (TETs) and has traditionally been performed via an open approach. Minimally invasive techniques have gained popularity with the aim of decreasing postoperative morbidity. However, there is concern that these techniques could increase the risk of local relapse. We undertook a retrospective institutional review of thymoma patients presenting for evaluation of local disease after surgery utilizing minimally invasive approaches. Methods: A database of TET patients evaluated at Indiana University from 1997 to 2022 was queried. From this database, we identified and reviewed 19 thymoma patients who underwent minimally invasive surgery and subsequently developed local recurrence. Results: The median age in this cohort was 46 years (range, 14–70 years) and included 9 female and 10 male patients. At the time of initial surgery, the distribution of stages was I (n=5), II (n=10), and III (n=3) and WHO histologic classifications were A/AB (n=3) and B1-3 (n=15); one patient’s initial pathology could not be determined. The median tumor size was 6.2 cm (range, 3–10.2 cm). Seventeen patients were operated on at outside institutions, while two had their surgeries at Indiana University. Surgical approaches included unilateral video-assisted thoracic surgery (VATS) (n=7), unilateral robot-assisted thoracic surgery (RATS) (n=8), bilateral VATS (n=2), and the Chamberlain procedure (n=2). Fifteen patients had R0 resections, while 4 had microscopic positive surgical margins (R1). Seven patients received adjuvant radiation therapy. All patients had pleural recurrence ipsilateral to the surgical approach. Ten patients also had mediastinal recurrence; 8 of whom had R0 resection during the initial surgery. The median time to recurrence was 31 months (range, 6–130 months). Conclusions: Our cohort of patients who presented for evaluation of thymoma recurrence after a minimally invasive surgical approach had median tumor size greater than 5 cm and higher World Health Organization (WHO) classifications. Relapses were identified as late as 10 years following surgery. While it remains unclear whether local recurrence was related to dissemination during surgery, the finding of ipsilateral pleural space relapse in all cases is strongly suggestive. This case series demonstrates the need for carefully controlled studies and long-term follow-up to determine optimal surgical approaches for thymoma.
A Refractory Stage IVb Thymoma Responded Completely to a Combination of Dasatinib and Prednisone but Poorly to Either One Alone
AbstractAbstract Abstract 4925 Introduction: Thymomas are rare tumors for which there is little randomized evidence to guide treatment and therefore, therapeutic options to cure advanced malignant thymomas are limited. We hereby report the first clinical outcome of combined dasatinib and prednisone therapy in a patient with heavily treated stage IVB malignant thymoma. Case Presentation: A 41 year old white male presented with fatigue, fever and granulocytopenia. He soon developed myasthenia gravis and aplastic anemia. Computer tomography showed a mediastinal mass, pleural thickening, splenomegaly and mesenteric nodes; biopsy of mediastinal mass revealed a malignant thymoma. Prednisone for 6 weeks along with antithymocyte globulin and cyclosporine were started for myasthenia gravis and aplastic anemia. Chemotherapy for unresectable thymoma was soon initiated with ADOC (Cisplatin, Doxorubicin, Vincristine, and Cyclophosphamide), but only small partial response was noted. After failing to show response to another three lines of therapy, we commenced therapy with dasatinib 75 mg twice daily. Thymoma showed partial response to dasatinib initially but soon became resistant and progressed. When prednisone 100 mg daily was added, a complete response was observed. Conclusion: A patient with stage IVB thymic carcinoma failed to respond well 3 lines of combination chemotherapy, and neither to prednisone or dasatinib alone. When dasatinib is combined with prednisone, it induced a complete response. Disclosures: Off Label Use: Dasatinib is an oral dual BCR/ABL and Src family tyrosine kinase inhibitor. It is a potent inhibitor of Imatinib resistant KIT activation loop mutants and induces apoptosis in mast cells and leukemic cells. At higher concentrations, Dasatinib also inhibits c-Kit, PDGFR and EphedrinA2. it has currently FDA approval for treatment of adults in all phases of chronic myeloid leukemias with resistance or intolerance to prior therapy, including Gleevec. The second indication for Dasatinib, is for the treatment of Ph+ALL. A number of Phase II trials have shown activity of this agent to various solid tumors including breast and lung cancer. Imatinib showed activity in thymomas, thus the rationale for using Dasatinib in the treatment of our patient.
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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