DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for malignant pleural mesothelioma — screening already-approved drugs against its 45-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleMalignant pleural mesothelioma maps to a 45-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 malignant pleural mesothelioma 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
dihydrofolate reductase (DHFR) — DHFR 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 ndpdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 4M6J · 1.201 Å · ligand NADPH DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE (NDP). Experimental structure, not a prediction.
What the evidence adds up to
Malignant pleural mesothelioma is a rare and aggressive tumour for which no effective therapy exists, despite the discovery of many possible molecular and genetic targets. The disease occurs in 2,000 to 3,000 people each year in the United States, and median overall survival ranges between 9 and 17 months regardless of stage. Prognosis has not significantly improved in recent decades. Asbestos is considered the major factor in pathogenesis, with more than 80% of patients having a history of asbestos exposure, and the latency period from exposure to diagnosis is typically 20–40 years, suggesting that multiple somatic genetic alterations are required for tumorigenic conversion of a mesothelial cell.
The clinical landscape has seen some progress, with major trials impacting treatment in both resectable and unresectable settings, and novel therapeutics have been discussed. However, the disease remains diffuse, with low median survival and prolonged latency presenting difficulty in prognosis, diagnosis, and treatment. Controversial issues persist, including the role of extrapleural pneumonectomy, adjuvant radiotherapy, and the use of intensity-modulated radiotherapy versus hemithoracic therapy. The late stage of diagnosis and the long latency between exposure and diagnosis have made it difficult to comprehensively evaluate the role of risk factors and their downstream molecular effects.
Advancements in next-generation sequencing and omics technologies have revolutionised genomics and medical diagnosis, and recent studies have explored the molecular mechanisms underlying the disease to identify potential therapeutic targets. Technologies and protocols to test new compounds in a more individualised manner are being developed, and these developments are expected to improve prognosis. Despite this, the review of all aspects of the disease underlines how much work remains to be carried out to improve prognosis and treatment.
What is still missing is a therapy that demonstrably improves overall survival in unselected patients. The heterogeneity of the disease means that patient stratification by molecular or genetic subtype is not yet standard in the clinic, and trials that test compounds in a more individualised manner are still in development. Adequate funding for such stratified trials, and for the validation of the many molecular and genetic targets that have been discovered, remains a barrier.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Journal of Clinical Oncology · 2009 · 480 citations
Malignant Pleural Mesothelioma
AbstractMalignant pleural mesothelioma (MPM) is a deadly disease that occurs in 2,000 to 3,000 people each year in the United States. Although MPM is an extremely difficult disease to treat, with the median overall survival ranging between 9 and 17 months regardless of stage, there has been significant progress over the last few years that has reshaped the clinical landscape. This article will provide a comprehensive discussion of the latest developments in the treatment of MPM. We will provide an update of the major clinical trials that impact mesothelioma treatment in the resectable and unresectable settings, discuss the impact of novel therapeutics, and provide perspective on where the clinical research in mesothelioma is moving. In addition, there are controversial issues, such as the role of extrapleural pneumonectomy, adjuvant radiotherapy, and use of intensity-modulated radiotherapy versus hemithoracic therapy that will also be addressed in this manuscript.
Expert Review of Anticancer Therapy · 2016 · 13 citations
A catalogue of treatment and technologies for malignant pleural mesothelioma
AbstractMalignant pleural mesothelioma is an aggressive fatal malignancy with a prognosis that has not significantly improved in the last decades. This review summarizes the current state of treatment and the various attempts that are made to improve overall survival for patients with malignant pleural mesothelioma. It also discusses technologies and protocols to test new and hopefully more effective compounds in a more individualized manner. These developments are expected to improve the prognosis for this group of patients.
Journal of Carcinogenesis · 2008 · 8 citations · open access
Pathogenesis of malignant pleural mesothelioma and the role of environmental and genetic factors
AbstractMalignant pleural mesothelioma (MPM) is a rare, aggressive tumor for which no effective therapy exists despite the discovery of many possible molecular and genetic targets. Many risk factors for MPM development have been recognized including environmental exposures, genetic susceptibility, viral contamination, and radiation. However, the late stage of MPM diagnosis and the long latency that exists between some exposures and diagnosis have made it difficult to comprehensively evaluate the role of risk factors and their downstream molecular effects. In this review, we discuss the current molecular and genetic contributors in MPM pathogenesis and the risk factors associated with these carcinogenic processes.
Pleural Mesothelioma: Treatable Traits of a Heterogeneous Disease
AbstractPleural mesothelioma is an aggressive disease with diffuse nature, low median survival, and prolonged latency presenting difficulty in prognosis, diagnosis, and treatment. Here, we review all these aspects to underline the progress being made in its investigation and to emphasize how much work remains to be carried out to improve prognosis and treatment.
IntechOpen eBooks · 2020 · 1 citations · open access
Genetic Alterations of Malignant Pleural Mesothelima
AbstractMalignant pleural mesothelioma (MPM) is a highly aggressive tumor that arises from the mesothelial cells lining the pleural cavity. Asbestos is considered the major factor in the pathogenesis of this malignancy, with more than 80% of patients with a history of asbestos exposure. MPM is characterized by a long latency period, typically 20–40 years from the time of asbestos exposure to diagnosis, suggesting that multiple somatic genetic alterations are required for the tumorigenic conversion of a mesothelial cell. In the last few years, advancements in next-generation sequencing and “–omics” technologies have revolutionized the field of genomics and medical diagnosis. The focus of this chapter is to summarize recent studies which explore the molecular mechanisms underlying this disease and identify potential therapeutic targets in MPM.
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.
