DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for Lung Sarcomatoid Carcinoma — 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 moduleLung Sarcomatoid Carcinoma 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 lung sarcomatoid carcinoma 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
NRAS proto-oncogene, GTPase (NRAS) — NRAS 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 gdpdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 6ZIO · 1.55 Å · ligand GUANOSINE-5'-DIPHOSPHATE (GDP). Experimental structure, not a prediction.
What the evidence adds up to
In a 2018 genomic study of four surgical cases, pulmonary sarcomatoid carcinoma was shown to evolve from a common ancestral clone, with the sarcomatous component branching off early from the carcinomatous component and accumulating a distinct set of mutations. All four tumours had strong PD-L1 staining (≥50%), and one case showed microsatellite instability. The authors suggested that high tumour mutation burden and strong PD-L1 expression might provide a rationale for targeted immunotherapies, but the sample size was four patients and no treatment outcomes were reported.
A retrospective analysis of 55 patients treated between 2011 and 2018 found a median survival of 12 months and overall survival rates of 52.7% at one year, 18.2% at two years, and 9.1% at three years. Most patients were male (76.4%), with a median age of 66 years, and about 60% presented with locally advanced or metastatic disease. Surgical resection was associated with better prognosis, and T stage was an independent prognostic factor on multivariate analysis. The study did not test any drug.
A 2017 case report described stepwise addition of genetic changes correlating with histological progression from well-differentiated carcinoma to sarcomatoid phenotype, based on targeted sequencing of 53 lung cancer-related genes in three distinct histological areas of a single tumour. The report noted that sarcomatoid cancers are characterised by poor prognosis and resistance to conventional chemotherapy, but no treatment data were presented.
A 2023 case report described a single patient with negative PD-L1 expression and low tumour mutation burden who received sintilimab combined with anlotinib and had a dramatic response. This is a single case, not a trial, and the drugs are not approved for this indication. What remains missing is prospective trial data with adequate sample sizes, validated biomarkers for patient stratification, and funding for randomised studies that could determine whether any immunotherapy or targeted approach improves survival over the natural history of 12 months median survival reported in the 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.
Oncotarget · 2018 · 47 citations · open access
New therapeutic targets for pulmonary sarcomatoid carcinomas based on their genomic and phylogenetic profiles
Abstract// Takahiro Nakagomi 1, 4 , Taichiro Goto 1, 4 , Yosuke Hirotsu 2 , Daichi Shikata 1 , Yujiro Yokoyama 1 , Rumi Higuchi 1 , Kenji Amemiya 2 , Kenichiro Okimoto 2 , Toshio Oyama 3 , Hitoshi Mochizuki 2 and Masao Omata 2, 5 1 Lung Cancer and Respiratory Disease Center, Yamanashi Central Hospital, Yamanashi, Japan 2 Genome Analysis Center, Yamanashi Central Hospital, Yamanashi, Japan 3 Department of Pathology, Yamanashi Central Hospital, Yamanashi, Japan 4 Keio University, Tokyo, Japan 5 University of Tokyo, Tokyo, Japan Correspondence to: Taichiro Goto, email: [email protected] Keywords: sarcomatoid cancer; lung cancer; mutation; next-generation sequencing; programmed death ligand-1 Received: July 06, 2017     Accepted: January 21, 2018     Published: January 31, 2018 ABSTRACT Objectives: Pulmonary sarcomatoid carcinomas are rare and generally aggressive tumors composed of carcinomatous and sarcomatous components; however, the evolution of sarcomatoid cancer has not been elucidated. Here, we aimed to evaluate the mutational profiles and phylogeny of sarcomatoid carcinomas using next generation sequencing and in-silico analysis to facilitate the development of novel therapies. Methods: Four patients who underwent surgery for sarcomatoid cancer were enrolled. Cancer cells were collected from carcinomatous and sarcomatous components in each tumor by laser capture microdissection. Next-generation sequencing was performed in each component, and the mutation profiles were compared. For further inference of phylogenies, phylogenetic and PyClone analyses were performed. Mismatch repair disturbance and programmed death ligand-1 (PD-L1) expression were also evaluated. Results: Comparative genetic analysis of different histological areas revealed that the separate components shared several common mutations, which showed relatively high cellular prevalence in the PyClone statistical inference. Phylogenetic analysis showed that the sarcomatous component had ramified from the carcinomatous component in the early phase of the evolution process and accumulated a number of mutations that were different from those of the carcinomatous component. Moreover, microsatellite instability was detected in a case of sarcomatoid cancer and PD-L1 was strongly positive (≥ 50%) in all sarcomatoid cancers. Conclusions: Our data suggest that sarcomatoid carcinoma evolves from a common ancestral clone, and its phylogenetic features may reflect high-grade malignancy in pulmonary sarcomatoid carcinoma. High tumor mutation burden and strong PD-L1 staining may provide a rationale for the use of targeted immunotherapies in pulmonary sarcomatoid carcinomas.
Frontiers in Oncology · 2022 · 12 citations · open access
Characteristics and Prognostic Analysis of 55 Patients With Pulmonary Sarcomatoid Carcinoma
AbstractPulmonary sarcomatoid carcinoma (PSC) is a rare and aggressive subtype of non-small-cell lung cancer (NSCLC). Here, we present information on the clinicopathologic characteristics and clinical outcomes of this type of cancer. Clinicopathologic data from 55 patients treated at a single cancer center from January 2011 to December 2018 were retrospectively analyzed. The patients were mostly male (76.4%), with a median age of 66 years and a history of smoking (54.5%). Most had symptoms, and about 60% presented with locally advanced or metastatic disease at diagnosis. Of the 55 cases, 21 were diagnosed by surgical resection. Pleomorphic cancer was the most common subtype (58.1%). With a median follow-up period of 13.2 months, the average survival time of the patients was 16.1 months, and the median survival time was 12 months. The overall survival rates for 1, 2, and 3 years were 52.7%, 18.2%, and 9.1%, respectively. Univariate analysis showed that prognosis of the patients was influenced by tumor size, T stage, metastatic status, and surgery ( p < 0.05). Multivariate analysis showed that T stage ( p = 0.034) was an independent prognostic factor. There are few reports on the natural history of PSC, and its clinicopathological characteristics remain unclear. Herein, a retrospective review 55 individuals with PSC found that T stage was an independent predictor of survival. Surgical resection was associated with better prognosis.
[Vandetanib treatment in refractory advanced lung adenocarcinoma patients: five cases and review of literature].
AbstractBACKGROUND AND OBJECTIVE: Vandetanib is a once-daily oral multi-target inhibitor of vascular endothelial growth factor receptor, epidermal growth factor receptor, and rearranged during transfection (RET) tyrosine kinases. The current study aimed to evaluate the effect and safety of vandetanib administered in refractory advanced lung adenocarcinoma patients. METHODS: Five patients who accepted chemotherapy and Tarceva therapy as first- and second-line treatments received vandetanib (300 mg, oral, once daily). RESULTS: The effects are stable disease on two patients (40%) and progressive disease on three patients (60%). With a median follow-up of 36 months, one patient remained on follow-up. The median progression free survival (PFS) is 2 months, and the mean overall survival is 22.6 months. The adverse events include rash (n=2), skin change (n=2), paronychia (n=2), asymptomatic QTc prolongation (n=2), ST-T change (n=1), diarrhea (n=1), and increased transaminase (n=1). CONCLUSIONS: There were lower incidences of severe side effects with vandetanib therapy in refractory advanced lung adenocarcinoma patients. The results of effect and safety of vandetanib are similar with the related reviewed articles.
Respirology Case Reports · 2025 · 2 citations · open access
Regorafenib Induced Interstitial Pneumonia in a Patient With Refractory Rectal Cancer
AbstractRegorafenib, a multi-targeted tyrosine kinase inhibitor (TKI), is indicated for refractory colorectal carcinoma, gastrointestinal stromal tumours (GIST), and hepatocellular carcinoma (HCC). We present a case involving a 66-year-old male patient with refractory colorectal cancer who developed interstitial pneumonia as a consequence of regorafenib therapy. Three months following the initiation of regorafenib administration, a chest computed tomography scan revealed bilateral ground-glass opacities, a characteristic finding in interstitial lung disease. This case illustrates a relatively rapid progression of regorafenib-induced interstitial lung disease following its radiographic manifestation. Clinicians should remain vigilant for this potential pulmonary toxicity in patients receiving regorafenib, even with an apparently short latency period after treatment commencement. Early recognition and prompt intervention are crucial in managing this adverse event.
Stepwise addition of genetic changes correlated with histological change from “well-differentiated” to “sarcomatoid” phenotypes: a case report
AbstractAbstract Background Sarcomatoid cancer is defined by the World Health Organization as a category of non-small cell lung cancers with sarcoma or sarcoma-like differentiation. They are characterized by poor prognosis and resistance to conventional chemotherapy. However, the mutational profile of sarcomatoid cancer remains yet to be elucidated. Sarcomatoid cancers are usually biphasic tumors composed of carcinomatous and sarcomatous components, but the evolutional development of sarcomatoid cancer is controversial. Case presentation We present an illustrative case of sarcomatoid cancer composed of three different histological areas. Targeted sequencing of 53 lung cancer-related genes was performed in each component and their phenotypic changes were correlated with stepwise addition of genetic changes. Conclusion Sarcomatous change of carcinoma occurs in the case of sarcomatoid cancer, and phenotypic changes to sarcomatoid cancer are associated with the addition of mutation patterns and derived from poorly differentiation tumor.
Open Journal of Clinical and Medical Case Reports · 2023 · 0 citations · open access
Dramatic response of a negative PD-L1 expression and TMB low pulmonary sarcomatoid carcinoma to sintilimab combined with anlotinib
AbstractPulmonary Sarcomatoid Carcinoma (PSC) is a rare and highly malignant subtype of Non Small Cell Lung Cancer (NSCLC). In contrast to other types of lung cancers, recent retrospective studies demonstrated that PSC always shows frequent genetic mutations, high TMB and high PD L1 expression which indicates these patients might derive survival benefits from immune checkpoint inhibitors
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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