DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for lung adenoma — screening already-approved drugs against its 20-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleLung adenoma maps to a 20-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 lung adenoma 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
fibroblast growth factor receptor 4 (FGFR4) — FGFR4 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 1~{r}drag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 8KH8 · 1.49 Å · ligand 1-[4-[(1~{R})-1-[3,5-bis(chloranyl)pyridin-4-yl]ethoxy]-5-cyano-pyridin-2-yl]-3-[6-methanoyl-5-[(4-methyl-2-oxidanylidene-piperazin-1-yl)methyl]-3-(2-morpholin-4-ylethoxy)pyridin-2-yl]urea (VVW). Experimental structure, not a prediction.
What the evidence adds up to
Lung adenocarcinoma is the most common and aggressive subtype of lung cancer, accounting for almost half of lung cancer deaths, and its incidence is rising globally in both sexes and in smokers and non-smokers. The disease does not arise spontaneously but through a stepwise progression from atypical adenomatous hyperplasia to adenocarcinoma in situ, minimally invasive adenocarcinoma, and finally frankly invasive adenocarcinoma. Despite advances in genomics and transcriptomics, the crucial early molecular events driving this evolution remain rudimentary, and the histological and molecular pathogenesis is still largely unknown. A 2013 high-throughput sequencing study comparing blood from lung adenocarcinoma patients with and without bone metastasis identified 7 down-regulated and 21 up-regulated microRNAs in the metastatic group, with 797 predicted target genes implicated in pathways such as MAPK, Wnt, and NF-kappaB, but this work offers no therapeutic intervention.
The clinical literature on adenomas of the lung is dominated by surgical case series rather than drug trials. A 1987 series of 29 bronchial adenoma patients reported no recurrence and a 5-year survival rate of about 96 per cent, but 62 per cent of patients required lobectomy or pneumonectomy because delayed diagnosis had led to total bronchial obstruction or destroyed parenchyma from recurrent infections; the authors state that earlier diagnosis would have allowed more conservative resections. A 1961 report of three childhood respiratory tract adenomas likewise stresses that delayed diagnosis caused prolonged morbidity and that surgical excision of tumour and damaged lung is the proper treatment. A 2016 case of a giant primary pleomorphic adenoma of the lung, presenting after chest trauma, was treated by surgical excision with a recommendation for lifelong follow-up. A 2019 review of atypical adenomatous hyperplasia notes that little literature exists on its treatment strategies and discusses surgery and stereotactic body radiotherapy for the rare patient who refuses surgery, but provides no drug data.
A 2017 study of seven pulmonary adenofibromas, benign fibroepithelial tumours, found a highly recurrent NAB2-STAT6 gene fusion (exon 4-exon 2) in the stromal but not epithelial component, alongside oestrogen receptor overexpression in 71 per cent of cases, demonstrating that these lesions share the molecular hallmark of solitary fibrous tumours. This finding clarifies the biology of a benign entity but has no bearing on drug repurposing for malignant disease. Across all abstracts, no drug, compound, or pharmacological agent is tested, named, or shown to alter the course of lung adenoma or adenocarcinoma.
What is missing is any clinical trial of a repurposed drug for lung adenoma or its precursor lesions, any prospective cohort with molecular stratification linking specific genetic alterations to drug response, and any funding mechanism to move beyond descriptive genomics and surgical case reports. The stepwise carcinogenesis model offers a theoretical window for prevention, but no abstract here provides evidence that any existing medicine can interrupt it, and the only outcome data available are surgical survival figures from small, retrospective series.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Respirology · 2011 · 76 citations
Pulmonary adenocarcinoma: A renewed entity in 2011
AbstractLung cancer, of which non-small-cell lung cancer comprises the majority, is the leading cause of cancer-related deaths in the United States and worldwide. Lung adenocarcinomas are a major subtype of non-small-cell lung cancers, are increasing in incidence globally in both males and females and in smokers and non-smokers, and are the cause for almost 50% of deaths attributable to lung cancer. Lung adenocarcinoma is a tumour with complex biology that we have recently started to understand with the advent of various histological, transcriptomic, genomic and proteomic technologies. However, the histological and molecular pathogenesis of this malignancy is still largely unknown. This review will describe advances in the molecular pathology of lung adenocarcinoma with emphasis on genomics and DNA alterations of this disease. Moreover, the review will discuss recognized lung adenocarcinoma preneoplastic lesions and current concepts of the early pathogenesis and progression of the disease. We will also portray the field cancerization phenomenon and lineage-specific oncogene expression pattern in lung cancer and how both remerging concepts can be exploited to increase our understanding of lung adenocarcinoma pathogenesis for subsequent development of biomarkers for early detection of adenocarcinomas and possibly personalized prevention.
OncoTargets and Therapy · 2020 · 44 citations · open access
<p>Rationale for Lung Adenocarcinoma Prevention and Drug Development Based on Molecular Biology During Carcinogenesis</p>
AbstractLung adenocarcinoma (LUAD) is the most common and aggressive subtype of lung cancer with the greatest heterogeneity and aggression. Inspite of recent years' achievements in understanding the pathogenesis of this disease, as well as the development of new therapeutic approaches, our knowledge on crucial early molecular events during its development is still rudimentary. Recent classification and grading of LUAD has postulated that LUAD does not arise spontaneously, but through a stepwise process from lung adenomatous premalignancy atypical adenomatous hyperplasia to adenocarcinoma in situ, minimally invasive adenocarcinoma, and eventually frankly invasive predominant adenocarcinoma. In this review, we discuss the molecular processes that drive the evolutionary process that results in the formation of LUAD. We also describe how to handle lung premalignancy in clinical settings based on the most recent advances in genomic biology and our own understanding of lung cancer prevention.
Recurrent <i><scp>NAB</scp>2</i>–<i><scp>STAT</scp>6</i> gene fusions and oestrogen receptor‐α expression in pulmonary adenofibromas
AbstractAIMS: Pulmonary adenofibromas are rare benign fibroepithelial tumours of the lung with unknown histogenesis and an indolent clinical behaviour. Their stroma resembles that of solitary fibrous tumours, whereas the glands are composed of respiratory epithelium organized in a phyllodes-like architecture. Differentiation of pulmonary adenofibromas from other more aggressive intrathoracic tumours is clinically relevant. However, their biology is unknown. Here, we sought to characterize pulmonary adenofibromas at a clinicopathological level and to define whether they could be underpinned by a highly recurrent somatic genetic alteration akin to tumours with similar morphology. METHODS AND RESULTS: Seven pulmonary adenofibromas were subjected to immunohistochemical analysis for thyroid transcription factor 1 (TTF1), napsin A, cytokeratin 7, E-cadherin, CD99, CD34, CD31, STAT6, oestrogen receptor (ER), progesterone receptor, androgen receptor, bcl-2, and vimentin, as well as electron microscopy and capillary sequencing on microdissected samples to evaluate the presence of NAB2-STAT6 fusion genes and MED12 exon 2 mutations in their discrete components. A control group comprising pulmonary solitary fibrous tumours, pulmonary hamartomas and breast fibroadenomas was also analysed. We confirmed that the stromal elements of pulmonary adenofibromas pertain to the fibroblastic lineage, and show ER overexpression in 71% of cases, whereas the epithelium consists of TTF1-positive, E-cadherin positive bronchiolar elements. A highly recurrent NAB2-STAT6 fusion variant (exon 4-exon 2) was detected in the stroma but not in the epithelium. No MED12 mutations were identified. CONCLUSIONS: Here, we demonstrate that pulmonary adenofibromas are neoplastic lesions harbouring the molecular hallmark of solitary fibrous tumours.
Genome-Wide Identification of Bone Metastasis-Related MicroRNAs in Lung Adenocarcinoma by High-Throughput Sequencing
AbstractBACKGROUND: MicroRNAs (miRNAs) are a class of small noncoding RNAs that regulate gene expression at the post-transcriptional level. They participate in a wide variety of biological processes, including apoptosis, proliferation and metastasis. The aberrant expression of miRNAs has been found to play an important role in many cancers. RESULTS: To understand the roles of miRNAs in the bone metastasis of lung adenocarcinoma, we constructed two small RNA libraries from blood of lung adenocarcinoma patients with and without bone metastasis. High-throughput sequencing combined with differential expression analysis identified that 7 microRNAs were down-regulated and 21 microRNAs were up-regulated in lung adenocarcinoma with bone metastasis. A total of 797 target genes of the differentially expressed microRNAs were identified using a bioinformatics approach. Functional annotation analysis indicated that a number of pathways might be involved in bone metastasis, survival of the primary origin and metastatic angiogenesis of lung adenocarcinoma. These include the MAPK, Wnt, and NF-kappaB signaling pathways, as well as pathways involving the matrix metalloproteinase, cytoskeletal protein and angiogenesis factors. CONCLUSIONS: This study provides some insights into the molecular mechanisms that underlie lung adenocarcinoma development, thereby aiding the diagnosis and treatment of the disease.
AbstractCase histories of three patients are reported, in whom adenomas of the respiratory tract produced dangerous prolonged morbidity in children before correct diagnosis was made. In all children with ususual wheezing disorders or recurrent pulmonary infections, the possible diagnosis of adenoma should be entertained. The proper treatment of adenomas of the respiratory tract in children is surgical excision of the tumor and of the permanently damaged lung tissue. Early diagnosis will reduce the incidence of pulmonary destruction and the possibility of metastasis.
The Thoracic and Cardiovascular Surgeon · 1987 · 12 citations
Surgical Treatment of Bronchial Adenomas: Results of 29 Cases and Review of the Literature
AbstractThe low-grade malignant potential of bronchial adenoma has been widely reported in the medical literature. During the past 12 years we have treated 29 patients with this disease, 18 (62%) of whom required conventional lobectomy or pneumonectomy, because most of our cases had come to our center after having inappropriate treatments in other centers and loosing time. In these cases we observed either a total obstruction of a bronchus or a destroyed parenchyma due to recurrent pulmonary infections. For this reason, the number of pulmonary resections is more important than conservative surgical procedures in our center. The other 11 cases (38%) were treated by bronchoplasty or more conservative resectional procedures. There was no recurrence and the survival rate was about 96 per cent at 5 years. We believe that, in our series, we would have mostly been able to perform conservative types of resections if we could have diagnosed the disease in its early stages.
Pulmonary Atypical Adenomatous Hyperplasia: Diagnostic and Therapeutic Implications
AbstractLung cancer still remains one of the most common cancers throughout the world, especially in smokers. Adenocarcinoma is now the predominant histological type in many western countries. The etiology of adenocarcinoma is unknown, but evidence suggests that atypical adenomatous hyperplasia (AAH) may act as a precursor lesion. Here we present two case reports of patients diagnosed with AAH on biopsy, highlighting 1) available treatment strategies and 2) AAH's progression to adenocarcinoma. A review of AAH is warranted as little literature is currently available regarding its treatment strategies, especially in light of its role as a precursor to adenocarcinoma. In this review, we will address the following topics: 1. What is the pathophysiology of AAH? 2. What is the natural history of AAH and its risk of malignant transformation? 3. When is surgery recommended? 4. What is the role of stereotactic body radiotherapy (SBRT) in the rare patient who refuses surgery?
Journal of Cardiothoracic Surgery · 2016 · 7 citations · open access
Giant primary pleomorphic adenoma of the lung presenting as a post-traumatic pulmonary hematoma: a case report
AbstractBACKGROUND: Pleomorphic adenomas, also known as benign mixed tumors, are the most common tumors of glandular origin in the head and neck and although they are generally benign they can undergo malignant transformation. Primary pleomorphic adenomas of the lung are extremely rare tumors with less than 40 cases reported in the literature by now. This is the first case in the literature describing overlapping with a traumatic event and also one of the rare cases describing primary adenoma of the lung reaching this impressive size. CASE PRESENTATION: We report a rare case of a giant primary pleomorphic adenoma of the lung presenting as a post-traumatic pulmonary hematoma. A 38-year-old Caucasian male patient came to the Urgent Trauma Center after being hit in the chest by a bull and, after a number of tests, was diagnosed with primary pleomorphic adenoma of the lung. Operative treatment was performed and the surgical excision was successfully done. CONCLUSIONS: Our conclusion is that the surgical excision is the main treatment for pleomorphic adenoma of the lungs and we recommend lifelong follow-up and regular check-ups. Furthermore, we consider our case an interesting one due to its concurrence with the chest trauma and the dilemma about the optimal approach considering the entity could have been a large interlobular hematoma.
Disease module: DeepOracle (Open Targets). Structures: RDKit from PubChem SMILES. Literature: retrieved by DeepSearch across 234,678,978 indexed works using Disease Ontology synonyms, 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.
