DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for Malignant Mesothelioma — screening already-approved drugs against its 14-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleMalignant Mesothelioma maps to a 14-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
approvedPemetrexedApproved drugapprovedMethotrexateApproved drug
Structures already discussed alongside malignant mesothelioma in the retrieved literature, rendered from public PubChem SMILES. Which drugs appear here reflects the evidence found, not a ranked prediction.
Molecular view
High resolution structure of TbPTR1 — Pemetrexed has a real, experimentally solved structure in complex with this target (PDB 2X9G, 1.1 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 lyadrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 2X9G · 1.1 Å · ligand Pemetrexed (LYA). Experimental structure, not a prediction.
What the evidence adds up to
Malignant mesothelioma in Germany has an incidence of about 20 cases per million persons per year, with a median latency of 50 years after asbestos exposure. In 2010, 1397 people died of the disease in Germany, and a plateau in incidence is predicted between 2015 and 2030. The prognosis remains poor, with a median survival time of only 12 months. The histological subtype and the Karnofsky score are the main prognostic factors. Most mesotheliomas arise from the pleura.
For many years, the only US Food and Drug Administration-approved first-line treatment for unresectable mesothelioma was pemetrexed plus cisplatin. The 2014 review states that early diagnosis is very difficult and that mesothelioma is mostly resistant to conventional therapies. The 2013 review notes that only limited data are available to guide treatment with a combination of chemotherapy, surgery, and radiotherapy, and that symptom control and preservation of quality of life are the main aspects of care.
The 2021 review reports the recent approval of nivolumab plus ipilimumab as frontline treatment for patients with pleural mesothelioma, calling this a significant milestone. It highlights the emerging use of immunotherapy and mesothelin-targeted therapies for the management of advanced, unresectable mesothelioma. The 2010 review summarises molecular defects involved in mesothelioma pathogenesis and progression, discussing genes that could be considered as biomarkers or therapeutic targets.
What is still missing is a clear understanding of the exact mechanism by which asbestos induces mesothelioma, as noted in the 2010 review. The 2014 review states that a host of factors may be responsible for drug resistance, but these processes are not yet fully understood. No randomised trial data are presented in these abstracts that show a survival benefit for any new combination beyond the approved checkpoint inhibitor regimen, and patient stratification by histological subtype or molecular markers remains an area of ongoing investigation rather than established practice.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Deutsches Ärzteblatt international · 2013 · 113 citations
Malignant Pleural Mesothelioma
AbstractBACKGROUND: The incidence of malignant mesothelioma in Germany is about 20 cases per million persons per year. Its association with asbestos exposure, usually occupational, has been unequivocally demonstrated. Even though the industrial use of asbestos was forbidden many years ago, new cases of mesothelioma continue to appear because of the long latency of the disease (median, 50 years). Its diagnosis and treatment still present a major challenge for ambulatory and in-hospital care and will do so for years to come. METHODS: This article is based on a selective review of the literature, along with data from the German Mesothelioma Register. RESULTS: 1397 people died of mesothelioma in Germany in 2010. A plateau in the incidence of the disease is predicted between 2015 and 2030. Most mesotheliomas arise from the pleura. The histological subtype and the Karnofsky score are the main prognostic factors. Only limited data are now available to guide treatment with a combination of the available methods (chemotherapy, surgery, radiotherapy). The prognosis is still poor, with a median survival time of only 12 months. Symptom control and the preservation of the patient's quality of life are the main aspects of care for patients with mesothelioma. CONCLUSION: The incidence of mesothelioma is not expected to drop in the next few years. The available treatments are chemotherapy, surgery, and radiotherapy. Specialized treatment centers now increasingly provide multimodal therapy for treatment of mesothelioma.
Current Opinion in Pulmonary Medicine · 2008 · 58 citations
Malignant mesothelioma 2008
AbstractPURPOSE OF REVIEW: Mesothelioma is an aggressive malignancy of the pleura with poor survival. There will be approximately 3000 cases of mesothelioma in the United States annually. Multimodality treatment including neoadjuvant chemotherapy in selected individuals followed by extrapleural pneumonectomy and radiation has been studied in recent trials for its effects on disease free and overall survival This review provides a general overview of malignant mesothelioma with a summary of the most significant articles from within the past year as well as from the past. RECENT FINDINGS: Areas of recent interest include the evaluation of osteopontin and mesothelin as new tumor markers for mesothelioma. New phase III trials have been performed to evaluate the use of combined chemotherapy regimens. SUMMARY: Malignant mesothelioma is a very difficult malignancy to treat. Patients with the disease usually have an occupational asbestos exposure, and in some, viral exposure with SV40. There have been many historical treatments including combinations of local control with surgery and radiation as well as attempts to prevent systemic failure with chemotherapy. Novel therapies including intrapleural chemotherapy, photodynamic therapy and hyperthermic perfusion have also been used with some success. Finally there are several attempts at immunomodulating and targeted treatments, which are in phase I/II trials.
High-dose methotrexate with citrovorum factor and vincristine in the treatment of malignant mesothelioma
AbstractThe incidence of malignant mesothelioma has increased greatly in the last 40 years. Current and recent past exposure to asbestos is expected to substantially increase this incidence. We report nine cases of malignant mesothelioma which temporarily responded to treatment with high-dose methotrexate-citrovorum rescue and vincristine. Further clinical trials of high-dose methotrexate with citrovorum rescue appear indicated in this disease.
Malignant mesothelioma: Advances in immune checkpoint inhibitor and mesothelin‐targeted therapies
AbstractMalignant mesothelioma is an aggressive cancer with a poor prognosis and limited treatment options. For many years, the only US Food and Drug Administration-approved first-line treatment for unresectable mesothelioma was pemetrexed plus cisplatin. However, the recent approval of nivolumab plus ipilimumab as frontline treatment for patients with pleural mesothelioma marks a significant milestone for the treatment of this disease. In this review, the authors describe recent advances in therapeutic strategies for the treatment of patients with advanced, unresectable mesothelioma, highlighting the emerging use of immunotherapy and mesothelin-targeted therapies for the management of malignant mesothelioma.
Biological Agents Involved in Malignant Mesothelioma: Relevance as Biomarkers or Therapeutic Targets
AbstractMalignant mesothelioma (MM) is a rare, highly aggressive tumor that arises from the surface serosal cells (pleural, peritoneal and pericardial cavities). Epidemiological and clinical data show that there is an association between asbestos exposure and MM development, even if the exact mechanism whereby asbestos induces MM is unknown. The continuing identification and elucidation of the molecular defects involved in mesothelioma pathogenesis and progression should lead to better disease control and greater therapeutic options in the near future. Goal of this article is to summarize the most recent advances in molecular pathogenesis of mesothelioma with particular emphasis on genes that could be considered as biomarkers or therapeutic targets and discuss possible clinical implications of these findings.
Journal of Cancer Science & Therapy · 2014 · 4 citations · open access
Current Therapies for Malignant Mesothelioma
AbstractMalignant mesothelioma (MM) is a deadly cancer caused by asbestos exposure that is increasing worldwide. Early diagnosis for this cancer is very difficult and MM is mostly resistant to conventional therapies. A host of factors may be responsible for development of MM and imparting drug resistance to this cancer. Understanding these processes will be important in designing therapeutic approaches for MM. Some of the conventional as well as current approaches for MM therapy are discussed in this review.
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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