DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for lung adenocarcinoma in situ — screening already-approved drugs against its 37-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleLung adenocarcinoma in situ maps to a 37-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 adenocarcinoma in situ 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
KRas proto-oncogene, GTPase (KRAS) — KRAS 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 7VVB · 1.7 Å · ligand PHOSPHOAMINOPHOSPHONIC ACID-GUANYLATE ESTER (GNP). Experimental structure, not a prediction.
What the evidence adds up to
Lung adenocarcinoma in situ (AIS) is understood as a pre-invasive stage in a proposed progression from atypical adenomatous hyperplasia (AAH) to AIS to minimally invasive adenocarcinoma (MIA). A targeted sequencing study of 5 AIS cases found that only one harboured mutated TP53 or EGFR, in contrast to MIA where 4 out of 5 cases had multiple EGFR alterations and 3 out of 5 had TP53 mutations. In AIS, only one patient carried a mutated APC gene, suggesting Wnt signalling plays an insignificant role at this stage. Instead, AIS carcinogenesis appeared to rely on alterations in the AKT pathway, with aberrations in KIT, KRAS, HRAS, IGF1R, FGFR3, MET or TSC2 found in 4 out of 5 patients. The same study sequenced 25 AAH lesions from 6 patients and found RAS and AKT/ERK pathways most frequently affected, and in 3 cases tracked a possible cancer-driving mutation from AAH to the primary tumour, providing a direct genetic link between the precursor lesion and adenocarcinoma.
A ten-year observational study of 471 patients with lung adenocarcinoma who underwent surgery reported a five-year survival rate of 76.23% for the entire cohort. No significant survival differences emerged between G1 and G2 tumours, but both showed markedly better survival than G3 tumours. Patients with spread through air spaces (STAS) had a lower survival rate than those without STAS. The study did not separately report outcomes for AIS patients, and AIS is typically considered to have an excellent prognosis after complete resection, but the data here aggregate all grades.
A single case report described a patient with lung adenocarcinoma who declined chemotherapy and radiotherapy and self-administered cannabidiol, a non-psychoactive cannabis compound. The authors reported a striking tumour response. This is a single uncontrolled observation and does not constitute evidence of efficacy for AIS or any other stage.
What is still missing are prospective trials specifically enrolling patients with AIS, which is now a distinct diagnostic category. No randomised data exist for any drug in AIS. The molecular pathways identified (AKT, RAS) suggest potential targets, but no targeted therapy has been tested in a dedicated AIS trial. The natural history of untreated AIS is not well characterised, and the rate of progression to invasive disease is unknown. Stratification by molecular subtype, long-term follow-up beyond five years, and standardised definitions of progression are all lacking.
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.
SAGE Open Medical Case Reports · 2019 · 35 citations · open access
Striking lung cancer response to self-administration of cannabidiol: A case report and literature review
AbstractIn spite of new drugs, lung cancer is associated with a very poor prognosis. While targeted therapies are improving outcomes, it is not uncommon for many patients to have only a partial response, and relapse during follow-up. Thus, new drugs or re-evaluation of existing therapies used to treat other non-malignant diseases (drug repurposing) are still needed. While this research both in vitro and in vivo is being carried out, it is important to be attentive to patients where the disease responds to treatments not considered standard in clinical practice. We report here a patient with adenocarcinoma of the lung who, after declining chemotherapy and radiotherapy, presented with tumour response following self-administration of cannabidiol, a non-psychoactive compound present in Cannabis sativa. Prior work has shown that cannabidiol may have anti-neoplastic properties and enhance the immune response to cancer. The data presented here indicate that cannabidiol might have led to a striking response in a patient with lung cancer.
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.
Novel insights into the molecular origins and treatment of lung cancer
AbstractLung cancer is the most common and most deadly cancer worldwide. Because of the aggressive and metastatic nature of many forms of the disease, it is frequently diagnosed late and responds poorly to the therapies currently available. Although our understanding of the molecular origins and evolution of lung cancer is still incomplete, recent research has yielded several developments that may offer opportunities for new, targeted and effective therapy. In this review we first discuss the prevalence and origins of lung cancer, with emphasis on non-small-cell lung cancer and adenocarcinoma, together with current treatments and their efficacy. We then look at a selection of recent papers which between them shed new light on possible therapeutic opportunities, including a novel synthetic interaction with the Kras gene and genomic or proteomic profiling studies that may pave the way for personalized treatment for lung cancer based on specific "signatures" of protein and gene expression. Lung cancer remains the foremost cause of cancer deaths worldwide. Despite advances in both detection and treatment, diagnosis is often late and the prognosis for patients poor. Our understanding of the molecular basis and progression of lung cancer remains incomplete, hampering the design and development of more effective diagnostic tools and therapies for this devastating disease. However, the last twelve months have witnessed the publication of several studies that represent significant advances in our knowledge of lung cancer, and may represent important steps on the road to effective new therapies. In this review we aim to summarize these recent developments, and give our perspectives on the therapeutic possibilities they may offer in the future.
Journal of Clinical Medicine · 2025 · 5 citations · open access
Ten-Year Observational Study of Patients with Lung Adenocarcinoma: Clinical Outcomes, Prognostic Factors, and Five-Year Survival Rates
AbstractBackground/Objectives: Lung carcinoma is the leading cause of cancer-related deaths globally, with lung adenocarcinoma being the most prevalent subtype. This study aims to review the clinical data and survival outcomes of patients diagnosed with lung adenocarcinoma who underwent surgical treatment. Methods: We retrospectively analyzed 471 patients (mean age 65.9 ± 7.81 years, range 38–86; 53.5% women) with histopathologically confirmed lung adenocarcinoma who underwent a lobectomy, bilobectomy, or pneumonectomy between May 2012 and December 2022. All patients were followed for up to five years post-surgery. Their medical histories, including previous neoplasms, comorbidities, tumor characteristics, and symptoms, were thoroughly reviewed. We calculated the overall survival rate and evaluated the impact of tumor grading and spread through air spaces (STAS) on patient outcomes. Results: The survival rate for the entire cohort was 76.23%. No significant survival differences emerged between G1 and G2 tumors, whereas both showed markedly better survival rates than G3 tumors. When these findings were applied to a simplified two-tier grading system (low grade vs. high grade), survival analyses showed a clear stratification of prognosis. Patients with STAS had a lower survival rate than those without STAS. Conclusions: Our findings indicate that a simplified grading system may improve prognostic evaluations for lung adenocarcinoma patients. Furthermore, STAS is a crucial factor affecting survival rates and should be considered in future treatment strategies. Expanding research in this area is essential to enhance treatment approaches for lung adenocarcinoma patients.
Abstract 1505: Targeted sequencing for the assessment of intratumor heterogeneity
AbstractAbstract Adenocarcinoma, the most common subtype of lung cancer, is notorious for eluding early detection. Thus, understanding the early steps of lung tumorigenesis at the genetic level might facilitate the development of more effective strategies for the prevention, early diagnosis, and treatment of lung cancer. Nearly 10% of lungs resected for adenocarcinomas harbored minute discrete foci of cytologically atypical bronchiolalveolar cells that are designated as atypical adenomatous hyperplasia (AAH). It has been postulated that these lesions represent an early stage in glandular neoplasia, which is now viewed as a progression from AAH to adenocarcinoma in situ (AIS) to minimally invasive adenocarcinoma (MIA), although, the biological nature of AAH is poorly understood and very controversial. To delineate tumor clonal heterogeneity as a function of tumor progression in early NSCLC neoplasias, we isolated DNA from different zones of histologic progression within the same lesion and performed targeted next generation sequencing which targets a panel of 134 well-characterized cancer and pharmacogenomics genes. We found that mutational landscape varies significantly between the three groups of patients. The most mutated genes in MIA were EGFR and TP53. 4 out of 5 MIA cases harbored multiple alternations in EGFR catalytic domain and inactivating mutations in TP53 were found in 3 out of 5 patients. Furthermore, mutations in Wnt pathway genes were found in 4 out of 5 cases. Notably, mutations/amplification in Notch family was detected in 3 out of 5 cases (predominantly in the tumor invasive zone). In contrast to MIA, in AIS, only one case out of 5 harbors mutated TP53 or EGFR. Unlike in MIA, only one AIS patient carried mutated APC gene, suggesting that Wnt signaling plays insignificant role in AIS carcinogenesis. On the contrary, we found that AIS carcinogenesis heavily relies on alternations of AKT pathway, since aberrations in KIT, KRAS, HRAS, IGF1R, FGFR3, MET or TSC2 genes were found in 4 out of 5 patients. For AAH cohort we sequenced 25 independent lesions from 6 patients. Sequencing revealed that RAS and AKT/ERK pathways were most frequently affected in these lesions. In 3 cases we were able to track a possible cancer driving mutation from AAH to the primary tumor. This observation provides for the first time a direct link between AAH lesion and primary adenocarcinoma. Most of the patients in all groups carried mutations in genes associated with DNA repair and chromatin remodeling, suggesting that deregulation of the DNA repair machinery is an early onset event of adenocarcinoma tumorigenesis. In all groups our analysis revealed mutations in genes that have been never implicated in lung adenocarcinoma. Our study helps to understand the potential role of heterogeneous clonal events in the progression of early glandular neoplasms including the transition from non-invasive to invasive disease. Citation Format: Eugene G. Izumchenko, Xiaofei Chang, Mariana Brait, William Westra, David Sidransky. Targeted sequencing for the assessment of intratumor heterogeneity. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1505. doi:10.1158/1538-7445.AM2014-1505
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.
