DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for renal pelvis carcinoma — screening already-approved drugs against its 3-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleRenal pelvis carcinoma maps to a 3-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 renal pelvis 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
von Hippel-Lindau tumor suppressor (VHL) — VHL 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 2s,4rdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 8QVU · 2.24 Å · ligand (2S,4R)-1-[(2S)-2-[4-[4-[(3S)-4-[4-[5-[(4S)-2-azanyl-3-cyano-4-methyl-6,7-dihydro-5H-1-benzothiophen-4-yl]-1,2,4-oxadiazol-3-yl]pyrimidin-2-yl]-3-methyl-1,4-diazepan-1-yl]butoxy]-1,2,3-triazol-1-yl]-3-methyl-butanoyl]-N-[(1R)-1-[4-(4-methyl-1,3-thiazol-5-yl)phenyl]-2-oxidanyl-ethyl]-4-oxidanyl-pyrrolidine-2-carboxamide (WYL). Experimental structure, not a prediction.
What the evidence adds up to
In a 2009 study of human urothelial carcinoma of the renal pelvis, a PI3K/AKT activation expression signature was identified in 76.9% of 13 tumour samples. Activating mutations of PIK3CA were found in 13.6% of 22 samples, and loss of heterozygosity at the PTEN locus in 25% of 8 samples. No PIK3CA mutations were found in 87 clear-cell renal cell carcinomas. Immunohistochemistry showed loss of PTEN protein expression in 36.4% of 11 samples and elevation of phosphorylated mTOR in 63.6% of 11 samples. In mice with biallelic inactivation of Pten in urogenital epithelia, 57.1% of animals older than one year developed renal pelvic urothelial carcinomas, and 15.8% of those with tumours had renal lymph node metastases. The authors suggested that inhibitors of the PI3K/AKT pathway, such as mTOR inhibitors, might be effective therapeutic agents, but no drug was tested in that study.
A 2024 case report describes a 69-year-old patient with stage IV urothelial carcinoma of the left renal pelvis (T2N0M1) and metastases to the bladder and right renal pelvis. The patient underwent transurethral resection of the bladder tumour, nephroureterectomy, and retroperitoneal lymphadenectomy in June 2023, then received six cycles of gemcitabine (1000 mg/m2 on days 1 and 8) plus carboplatin (AUC 5 on day 1) between July and October 2023. From November 2023, maintenance therapy with avelumab was given. No survival or response data are reported for this single patient.
A 2019 review of kidney tumour molecular pathology notes that renal cell carcinoma constitutes 90% of all kidney cancers, and that the 2016 World Health Organization classification has expanded subtypes based on molecular and morphological findings. The review states that complex molecular changes underlying renal cell carcinoma variants and corresponding familial cancer syndromes remain under investigation, especially for mechanism-based therapeutic approaches. No specific drug or trial data for renal pelvis carcinoma are provided.
What is still missing are prospective clinical trials testing PI3K/AKT/mTOR inhibitors specifically in renal pelvis urothelial carcinoma, with adequate sample sizes and defined patient stratification by PIK3CA mutation or PTEN loss status. The single case report provides no controlled evidence for the gemcitabine–carboplatin–avelumab regimen. Funding for such trials, as well as for molecular profiling of these rare tumours, remains 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.
Cancer Research · 2009 · 64 citations · open access
Activation of the PI3K/AKT Pathway Induces Urothelial Carcinoma of the Renal Pelvis: Identification in Human Tumors and Confirmation in Animal Models
AbstractUrothelial carcinoma of the renal pelvis is a deadly disease with an unclear tumorigenic mechanism. We conducted gene expression profiling on a set of human tumors of this type and identified a phosphatidylinositol 3-kinase (PI3K)/AKT activation expression signature in 76.9% (n = 13) of our samples. Sequence analysis found both activating mutations of PIK3CA (13.6%, n = 22) and loss of heterozygosity at the PTEN locus (25%, n = 8). In contrast, none of the other subtypes of kidney neoplasms (e.g., clear-cell renal cell carcinoma) harbored PIK3CA mutations (n = 87; P < 0.001). Immunohistochemical analysis of urothelial carcinoma samples found loss of PTEN protein expression (36.4%, n = 11) and elevation of phosphorylated mammalian target of rapamycin (mTOR; 63.6%, n = 11). To confirm the role of the PI3K/AKT pathway in urothelial carcinoma, we generated mice containing biallelic inactivation of Pten in the urogenital epithelia. These mice developed typical renal pelvic urothelial carcinomas, with an incidence of 57.1% in mice older than 1 year. Laser capture microdissection followed by PCR confirmed the deletion of Pten exons 4 and 5 in the animal tumor cells. Immunohistochemical analyses showed increased phospho-mTOR and phospho-S6K levels in the animal tumors. Renal lymph node metastases were found in 15.8% of the animals with urothelial carcinoma. In conclusion, we identified and confirmed an important role for the PI3K/AKT pathway in the development of urothelial carcinoma and suggested that inhibitors of this pathway (e.g., mTOR inhibitor) may serve as effective therapeutic agents.
Bilateral urothelial carcinoma of the renal pelvis
AbstractUrothelial carcinoma is the 4th most prevalent malignant tumor after prostate (or breast), lung and colorectal cancers. Urothelial carcinoma of the upper urinary tract is quite rare and accounts for 5–10 % of all cases of this type of cancer. Tumors of the renal pelvis are 2 times more common than tumors of the ureter. A clinical case of a 69-year-old patient diagnosed with urothelial carcinoma of the left renal pelvis T2N0M1, stage IV and metastases into the bladder, right renal pelvis is presented. On 08.06.2023, the patient underwent transurethral resection of the bladder tumor, ureteric orifice, nephroureterectomy on the left, retroperitoneal lymphadenectomy. Between 07.2023 and 10.2023, the patient received 6 cycles of chemotherapy according to the following scheme: gemcitabine 1000 mg/m2 intravenously on the 1st and 8th days ++ carboplatin AUC 5 intravenously on the 1st day. Since 11.2023, the patient in receiving maintenance therapy with avelumab.
AbstractRenal cell carcinoma constitutes 90% of all kidney cancers. Familial/genetic cause accounts for 2–4% of the cases and the rest of them are sporadic. The classification of renal cell carcinoma has been expanded since the first Heidelberg classification in 1997. The recently published 2016 World Health Organization classification has revealed several renal cell carcinoma subtypes according to the molecular and morphological investigations. The complex molecular changes underlying renal cell carcinoma variants and the corresponding familial cancer syndromes still remain the subject of ongoing investigations, especially for the mechanism-based therapeutic approaches. In this section, the molecular pathways and molecular features of each renal cell carcinoma subtype and the corresponding hereditary forms are reviewed.
Clinical case of locally advanced renal cell carcinoma with an inferior vena cava tumor thrombus treated with VEGFR-TKI/IO combination pembrolizumab + lenvatinib
AbstractThe article presents a clinical case of treatment of a young man with locally advanced renal cell carcinoma with an inferior vena cava tumor thrombus above the diaphragm. Due to non-standard neoadjuvant approach of using modern tyrosine kinase inhibitors of VEGFR and immunotherapy (VEGFR-TKI/IO) combination pembrolizumab + lenvatinib, thoracotomy was avoided and complete pathological regression of the tumor was achieved. Various studies on neoadjuvant therapy of kidney cancer including in patients with tumor thrombus are discussed, and the prospects for introducing this approach into clinical practice are described.
Recenti Progressi in Medicina · 2018 · 0 citations · open access
Attività ed efficacia di vinflunina in terza linea in paziente con carcinoma uroteliale avanzato della pelvi renale, in progressione a immunoterapia
AbstractThe clinical case concerns a 72-years-old woman diagnosed with an urothelial carcinoma of the renal pelvis with hepatic and lymph node metastases. The disease was rapidly progressing to a first line of platinum-based chemotherapy and to a second line with immunotherapy; a clinical and instrumental benefit was then observed with vinflunine used as third line regimen.
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.
