DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for hereditary renal cell carcinoma — screening already-approved drugs against its 5-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleHereditary renal cell carcinoma maps to a 5-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 hereditary renal cell 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
deoxyribonuclease 1 (DNASE1) — DNASE1 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 2-hydroxy-ethyldrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 4AWN · 1.95 Å · ligand 2-[BIS-(2-HYDROXY-ETHYL)-AMINO]-2-HYDROXYMETHYL-PROPANE-1,3-DIOL (BTB). Experimental structure, not a prediction.
What the evidence adds up to
Hereditary leiomyomatosis and renal cell cancer (HLRCC) is a hereditary cancer syndrome in which affected individuals are at risk for cutaneous and uterine leiomyomas and kidney cancer. In a 2007 study of 19 patients with HLRCC-associated renal tumours (11 women, 8 men; median age at diagnosis 39 years), the median pathological tumour size was 7.8 cm (range 1.5 to 20). Four of seven patients with T1 tumours (2.0 to 6.7 cm) had spread to regional lymph nodes or metastases at nephrectomy. Overall, 9 of 19 patients (47%) presented with nodal or distant metastases. The authors concluded that renal tumours in HLRCC are significantly more aggressive than those in other hereditary renal tumour syndromes, and that the standard 3 cm threshold for observation used in other familial syndromes is not recommended for HLRCC.
Hereditary kidney cancer syndromes account for only about 5% to 8% of all kidney cancers, but should be considered in anyone with an early age of onset. Most specific tumour syndromes are associated with a histopathologically distinct renal cell tumour phenotype. The recognition of patients with hereditary renal cell carcinoma and the identification of family members at higher risk is important for early tumour detection and treatment. Conservative management strategies have been developed to limit treatment-related morbidity, and knowledge of genetic alterations can dictate when and how to intervene surgically.
Despite these advances, significant work remains to fully delineate management strategies for young individuals with and without hereditary cancer syndromes. The abstracts provide no data on any drug treatment or systemic therapy for HLRCC. What is still missing are prospective trials testing targeted agents or repurposed drugs specifically in HLRCC patients, adequate funding for such trials given the rarity of the syndrome, and validated biomarkers to stratify patients by risk of early metastasis.
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 Journal of Urology · 2007 · 282 citations
Hereditary Leiomyomatosis and Renal Cell Cancer: A Syndrome Associated With an Aggressive Form of Inherited Renal Cancer
AbstractPURPOSE: Hereditary leiomyomatosis and renal cell cancer is a recently described hereditary cancer syndrome in which affected individuals are at risk for cutaneous and uterine leiomyomas, and kidney cancer. Our initial experience revealed the aggressive behavior of these renal tumors, often with early metastasis, despite small primary tumor size. We report the clinical characteristics and urological treatment of patients with hereditary leiomyomatosis and renal cell cancer associated renal tumors. MATERIALS AND METHODS: A total of 19 patients with hereditary leiomyomatosis and renal cell cancer associated renal tumors were evaluated. The 11 women and 8 men had a median age at diagnosis of 39 years (range 22 to 67), and a median clinical and radiological followup of 34 months (range 6 to 141). Hereditary leiomyomatosis and renal cell cancer manifestations in patients with renal tumors included cutaneous leiomyomas in 11 of 17 evaluable patients (65%) and uterine leiomyomas in 7 of 7 evaluable females (100%). RESULTS: Median pathological tumor size was 7.8 cm (range 1.5 to 20). Histological subtypes were consistent with hereditary leiomyomatosis and renal cell cancer renal carcinoma. Four of 7 patients with 2.0 to 6.7 cm T1 tumors had spread to regional lymph nodes or metastases at nephrectomy. Overall 9 of 19 patients (47%) presented with nodal or distant metastases. CONCLUSIONS: Renal tumors in patients with hereditary leiomyomatosis and renal cell cancer syndrome are significantly more aggressive than those in patients with other hereditary renal tumor syndromes. In contrast to other familial renal cancer syndromes, the observation of 3 cm or less renal tumors associated with hereditary leiomyomatosis and renal cell cancer is not recommended. Careful followup of affected and at risk individuals in families is necessary.
AbstractPURPOSE OF REVIEW: Changing strategies in the evaluation and treatment of renal neoplasms have been fostered by developments in the understanding of the genetics and molecular biology of renal tumors. Many of these discoveries have come from research into hereditary kidney cancer syndromes and the genetic mutations responsible for tumorigenesis. The purpose of this review is to familiarize the reader with the known heritable forms of kidney cancer, the recent advances in the field and their impact on patient management. RECENT FINDINGS: Genetic and phenotypic characterization of renal cancer syndromes includes von Hippel-Lindau disease, Birt-Hogg-Dube syndrome, hereditary papillary renal carcinoma, and hereditary leiomyomatosis and renal carcinoma. SUMMARY: Hereditary kidney cancer syndromes offer valuable insight into the pathogenesis of kidney cancer through identification of the underlying genetic mechanisms common to hereditary and sporadic forms of disease. An understanding of the manifestations of these diseases is necessary to allow for accurate diagnosis of patients and to provide the opportunity for appropriate screening. Conservative management strategies have been developed and should be followed to limit treatment-related morbidity.
Precision Surgery and Kidney Cancer: Knowledge of Genetic Alterations Influences Surgical Management
AbstractRenal cell carcinoma is a term that represents multiple different disease processes, each driven by different genetic alterations, with distinct histology, and biological potential which necessitates divergent management strategies. This review discusses the genetic alterations seen in several forms of hereditary kidney cancer and how that knowledge can dictate when and how to intervene with a focus on the surgical management of these tumors.
Management of renal cell carcinoma in young patients and patients with hereditary syndromes
AbstractPURPOSE OF REVIEW: Individuals that present with renal cell carcinoma at an early age deserve special attention because they are more likely to harbor an inherited predisposition and may require unique treatment strategies. RECENT FINDINGS: In recent years, there has been a significant increase in the number of characterized hereditary syndromes, many of which may predispose to kidney cancer. Although hereditary kidney cancer accounts for only 5-8% of kidney cancers, it should be considered in anyone with an early age of onset. These uncommon presentations should prompt consideration for genetic evaluation for germline alterations or somatic alterations associated with translocations. Treatment of kidney cancer in young individuals must also consider the late risks of nephron loss, the uncertainty with long-term follow-up after ablation, and the need for years of surveillance not only for the treated tumor but for de novo lesions in a patient with a greater risk of multifocality. SUMMARY: Early age of onset should raise concern for a hereditary renal cell carcinoma syndrome and should prompt consideration for genetic counseling to review personal and family history and determine if testing is indicated. Despite advancements in this field, significant work remains to fully delineate the management strategies for young individuals with and without hereditary cancer syndromes.
AbstractRecent advances in molecular genetics have elucidated the biological mechanisms of familial renal cell carcinoma (RCC), which have been responsible for the development and introduction of novel targeted agents that continue to change and refine the management of advanced disease. The genetic pathways have been well characterized and defined for several hereditary kidney cancer syndromes, including von Hippel–Lindau, hereditary papillary RCC, Birt–Hogg–Dubè, and hereditary leiomyomatosis RCC. Each of these hereditary kidney cancer syndromes has distinct clinical manifestations and treatment challenges. In this context, our objective is to provide an overview of the molecular genetics, clinical syndromes, and management strategy of hereditary kidney cancer syndromes.
[Hereditary renal tumors: More common than expected?].
AbstractRenal cell carcinomas are associated with hereditary tumor syndromes in approximately 5 % of cases. In patients with a hereditary predisposition, tumors show an earlier age of onset, often with a multicentric and bilateral manifestation. While some patients with renal cell carcinoma can be classified into well-characterized kidney cancer syndromes others have a genetic background which is still poorly understood. Most of the specific tumor syndromes are associated with a histopathologically distinct renal cell tumor phenotype. The recognition of patients with hereditary renal cell carcinoma and the identification of individual family members with a higher risk of development of renal tumors is important for early tumor detection and treatment. This manuscript reviews the clinical pathological and molecular findings of hereditary renal cell carcinoma syndromes.
Laboratory Investigation · 2016 · 2 citations · open access
Establishment and characterization of BHD-F59RSVT, an immortalized cell line derived from a renal cell carcinoma in a patient with Birt–Hogg–Dubé syndrome
AbstractHereditary renal cell carcinomas (RCCs) are life-threatening disorders not only for the patients but also for their relatives. Birt-Hogg-Dubé syndrome (BHD) is an autosomal dominant disorder caused by germline mutations in the folliculin gene (FLCN). The protein product, FLCN, functions as a tumor suppressor, and the affected patients have high risks of developing multiple RCCs. The carcinogenic mechanisms stemming from FLCN dysfunction have been investigated using rodent models and human RCC tissues. However, very limited information has been available about in vitro signaling of human renal cells with genetically mutant FLCN. Herein, we established a new cell line, BHD-F59RSVT, from a BHD patient's chromophobe RCC by transfecting SV40 large T antigen. We investigated FLCN mutations, chromosome profiles, and cytopathologic characteristics of the cell line. BHD-F59RSVT reflected the patient's FLCN germline mutation, a 3-nt deletion in exon 13 (c.1528_1530delGAG). Neither somatic mutation nor loss of heterozygosity of FLCN was detectable. Chromosome 17p11.2 of the FLCN proximal region demonstrated a trimodal pattern. Genome-wide chromosomal analysis revealed a loss of chromosome 16 and mosaic segmental gains in chromosome 7. BHD-F59RSVT cells were positive when immunostained for cytokeratin 7, supporting their origin from distal convoluted tubules. Western blotting analysis demonstrated severely suppressed FLCN expression at the protein level. The collective findings indicate that the established cell line will be suitable for functional analysis of the typical phenotype of BHD-associated RCC with suppressed FLCN expression.
Clinical journal of oncology nursing · 2020 · 0 citations
Renal Cell Cancer Syndromes: Identification and Management of Patients and Families at Increased Risk
AbstractThere are many inherited renal cell cancer syndromes that increase an individual's risk of developing renal cell cancer. The age of onset for these renal cell cancer syndromes ranges from infancy to age 65 years. Clinical manifestations vary widely, and multiple body systems can be involved and present unique challenges to the healthcare team. With the advancement of genetic panels, clinicians can screen individuals with known hereditary syndromes for genetic mutations. This article offers clinically relevant information specific to various major renal cell cancer syndromes.
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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