DeCure's autonomous Nephrology AI scientist is researching a drug-repurposing hypothesis for kidney oncocytoma — screening already-approved drugs against its 25-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleKidney oncocytoma maps to a 25-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 kidney oncocytoma 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
CREB binding lysine acetyltransferase (CREBBP) — CREBBP 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 1vudrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 9H0K · 1.75 Å · ligand propionyl Coenzyme A (1VU). Experimental structure, not a prediction.
What the evidence adds up to
Renal oncocytoma is a distinct renal tumour considered to have low malignant potential, but its diagnosis and clinical behaviour are complicated by overlapping features with other renal lesions. A 1984 review of 562 surgically removed renal cell carcinomas or adenomas identified 18 oncocytomas, and among 112 renal cell tumours from 8489 autopsies, 12 oncocytomas were found; all tumours behaved in a benign fashion despite large size or moderate histological atypia, and immunoperoxidase staining for alpha-1-antichymotrypsin was positive in all tumours studied, suggesting origin from proximal tubular cells. A 1991 Australian review of 24 cases seen between 1978 and 1989 found considerable overlap in clinical presentation between oncocytomas and renal carcinomas, and concluded that pre-operative radiological, cytological and pathological investigations cannot make a definitive diagnosis, recommending that these tumours be treated as potential renal carcinomas until post-operative microscopic evaluation proves otherwise.
Genetic analysis has identified consistent chromosomal losses in oncocytomas. A 1996 comparative genomic hybridisation study of 13 renal oncocytomas found loss of genetic material from chromosomes 1 and/or 14 in six tumours, which the authors suggested may represent early genetic events in tumour development. A 2013 study reviewing 53 consecutive renal oncocytomas identified a telangiectatic variant accounting for 15% of cases, with tumours ranging from 2.4 to 6.0 cm (mean 3.5 cm), presenting as enhancing masses suspicious for or consistent with renal malignancy on radiology, and characterised microscopically by variably sized blood-distended spaces lined by typical oncocytoma cells without degenerative changes.
The relationship between oncocytoma and tuberous sclerosis complex is more complex than previously believed. A 1998 study of five tumours previously reported as renal cell carcinoma in tuberous sclerosis patients found that only one showed an immunohistochemical phenotype indicative of an epithelial tumour (Ker+, HMB45-); three exhibited a phenotype compatible with the monotypic epithelioid variant of angiomyolipoma (HMB45+, Ker-), and two of those three patients died of metastatic disease. The authors concluded that renal cell carcinoma is less common in tuberous sclerosis complex than previously believed, that some cases called renal cell carcinoma probably represent a monotypic epithelioid variant of angiomyolipoma, and that epithelioid angiomyolipoma is a potentially malignant tumour with invasion and metastases. A 2001 case report described a 53-year-old man with end-stage renal disease requiring haemodialysis whose kidneys contained more than 100 oncocytomas and an associated papillary renal cell carcinoma in the right kidney.
What remains missing is a reliable pre-operative diagnostic method that can distinguish oncocytoma from renal cell carcinoma, as current radiological, cytological and pathological investigations cannot do so definitively. The natural history of the telangiectatic variant and its long-term outcomes are not established, and the genetic events driving oncocytoma formation beyond the observed chromosome 1 and 14 losses are not characterised. No data exist on systemic therapy for oncocytoma, and the clinical significance of oncocytomas arising in the setting of tuberous sclerosis or renal failure syndromes remains unclear, with no prospective studies addressing surveillance or intervention strategies for these patients.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
The American Journal of Surgical Pathology · 1998 · 263 citations
Apparent Renal Cell Carcinomas in Tuberous Sclerosis Are Heterogeneous
AbstractRenal epithelial tumors (carcinoma and oncocytoma) have been reported with higher a frequency than expected in patients with the tuberous sclerosis complex. However, the recent identification of a monotypic, epithelioid variant of angiomyolipoma, closely simulating renal cell carcinoma, has cast doubt on the real frequency of carcinoma. Immunohistochemical analysis with a panel of antibodies, including melanogenesis marker HMB45, can discriminate between carcinoma and carcinoma-like angiomyolipoma. We studied five tumors previously reported as carcinoma and found that only one of them showed an immunohistochemical phenotype indicative of an epithelial tumor (Ker+, HMB45-). Three tumors exhibited a phenotype compatible with the monotypic epithelioid variant of angiomyolipoma (HMB45+, Ker-), and two of the three patients died of metastatic disease. The last patient had unusual clinical features, and the tumor was positive both for HMB45 and keratin. It is concluded that (1) renal cell carcinoma is less common in tuberous sclerosis complex than previously believed, (2) some cases called renal cell carcinoma probably represent a monotypic, epithelioid variant of angiomyolipoma, and (3) epithelioid angiomyolipoma is a potentially malignant tumor with invasion and metastases. These findings indicate that all reported renal carcinomas in tuberous sclerosis complex, therefore, must be reevaluated.
Genes Chromosomes and Cancer · 1996 · 68 citations
Comparative genomic hybridization for genetic analysis of renal oncocytomas
AbstractRenal oncocytomas are uncommon tumors of the kidney that are considered to be of low malignant potential. Neither conventional cytogenetic nor restriction fragment length polymorphism analyses have identified consistent genetic alterations in their genomic DNA. The purpose of the present study was to identify the genetic alterations associated with the development of renal oncocytomas. We studied 13 renal oncocytomas by using comparative genomic hybridization, and we identified loss of genetic material from chromosomes 1 and/or 14 in six of these tumors. These alterations may represent early genetic events in the development of these tumors.
Renal oncocytoma: the incidence of 18 surgical and 12 autopsy cases
AbstractThe material of 562 surgically removed renal cell carcinomas or adenomas was reviewed, and 18 tumors were diagnosed as renal oncocytomas. The incidence seemed to increase strikingly during recent years. Similarly, among 112 renal cell tumours from 8489 autopsies, 12 oncocytomas were found. Immunoperoxidase staining for alpha-I-antichymotrypsin was positive in all the tumours studied speaking for the origin from proximal tubular cells. All the tumours behaved in a benign fashion despite the large size and/or moderate histological atypia. The recognition of renal oncocytoma is urged, because its incidence seems to be increasing, and the prognosis is much better than that of renal cell carcinoma.
Archives of Pathology & Laboratory Medicine · 2001 · 29 citations
Bilateral Renal Oncocytosis With Renal Failure
AbstractOncocytosis is a term recently used to describe diffuse renal involvement by numerous oncocytic nodules. We report herein a case of a 53-year-old man with end-stage renal disease requiring hemodialysis. His kidneys were involved by numerous tumors. Histologic examination revealed more than 100 oncocytomas and an associated papillary renal cell carcinoma in the right kidney.
AbstractA review was made of 24 cases of renal oncocytoma seen between 1978 and 1989. There was considerable overlap between the clinical presentation of renal oncocytomas and renal carcinomas. Although pre-operative radiological, cytological and pathological investigations may suggest the presence of an oncocytoma, these studies cannot make a definitive diagnosis. We recommend that these tumours be treated as potential renal carcinomas until post-operative microscopic evaluation proves otherwise.
American Journal of Clinical Pathology · 2013 · 11 citations · open access
Telangiectatic Oncocytoma
AbstractOBJECTIVES: To identify, describe, and investigate the clinical, radiologic, and pathologic features of 8 cases of telangiectatic oncocytoma. METHODS: Fifty-three consecutive renal oncocytomas were reviewed for the telangiectatic pathologic features that were subsequently correlated with the demographic, clinical, and radiographic findings. RESULTS: Telangiectatic oncocytoma accounted for 15% of the 53 renal oncocytomas collected in the past 7 years in our institution. On radiology, almost all presented as an enhancing mass and were suspicious for or consistent with a renal malignant tumor. Grossly, the tumors ranged from 2.4 to 6.0 cm (mean, 3.5 cm) and macroscopically were hemorrhagic spongy or multicystic masses without a central stellate scar. Microscopically, they were characterized by variably sized blood-distended spaces (<0.1-mm to 2- to 3-mm blood lakes) lined by typical oncocytoma cells and without evidence of degenerative changes. CONCLUSIONS: With its unique radiologic and pathologic presentations in comparison with classic renal oncocytoma, it is important to recognize this new variant of renal oncocytoma.
The Medical Journal of Australia · 1985 · 8 citations
Renal oncocytoma: a benign tumour on the increase
AbstractRenal oncocytoma is an uncommon tumour which is being diagnosed with increasing frequency in recent years. Traditionally, these renal tumours were considered to be histological variants of renal adenocarcinomas, with no prognostic significance of their own. Several recent retrospective studies have demonstrated that they are a separate benign entity; therefore, differentiation and identification of these tumours are of the utmost importance.
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.
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