DeCure for Hereditary papillary renal cell carcinoma
DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for hereditary papillary renal cell carcinoma — screening already-approved drugs against its 1-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleHereditary papillary renal cell carcinoma maps to a 1-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 papillary 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
MET proto-oncogene, receptor tyrosine kinase (MET) — MET 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 sulfoaminodrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 7MO9 · 4.0 Å · ligand 2-deoxy-6-O-sulfo-2-(sulfoamino)-alpha-D-glucopyranose (SGN). Experimental structure, not a prediction.
What the evidence adds up to
Hereditary papillary renal carcinoma is a rare autosomal dominant disease caused by activating mutations in the MET gene. A 2020 case report describes a 28‑year‑old Russian woman with no family history of hereditary cancer syndromes who had 7 primary papillary type I renal cell carcinomas in the left kidney and 10 in the right kidney. The tumours were resected in a two‑step surgical procedure, and at follow‑up in February 2019 no sign of disease progression was detected. Molecular genetic analysis identified a germline heterozygous missense variant in MET: c.3328G>A (p.V1110I; CM990852). The authors discussed the biological effects of that mutation and the utility of DNA diagnostics for treating patients with hereditary papillary renal carcinoma.
A 1996 letter notes that affected family members have a predisposition for multiple papillary tumours in both kidneys, and that a long interval often passes between detection of papillary renal carcinoma in an individual family member and referral of the family to a major cancer genetics centre. In one family pedigree, papillary renal carcinoma was detected in the first member in 1971 and in the second in 1984; the family was referred to the National Cancer Institute in 1995, by which time five members had developed the disease. In a Canadian family, the initial diagnosis was in 1978, and other members were diagnosed in 1980, 1980, 1984, 1985, 1987, 1990, 1990 and 1995; von Hippel‑Lindau disease was incorrectly diagnosed in 1990. The letter states that any family in which two members have papillary renal carcinoma should be referred to a cancer genetics centre for further study and evaluation.
A 2021 review discusses how knowledge of genetic alterations in several forms of hereditary kidney cancer can dictate when and how to intervene surgically, but does not report any drug treatment or clinical trial data for hereditary papillary renal cell carcinoma. No abstract in this set provides any information on systemic therapy, response rates, survival, or repurposed drugs for this disease.
What is still missing is any funded clinical trial testing a drug—repurposed or otherwise—specifically for hereditary papillary renal cell carcinoma, a trial design that accounts for the multiple, bilateral tumours and the long natural history of the disease, and patient stratification by the specific MET mutation present.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Genes · 2021 · 28 citations · open access
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.
Frontiers in Oncology · 2020 · 12 citations · open access
Case of Hereditary Papillary Renal Cell Carcinoma Type I in a Patient With a Germline MET Mutation in Russia
AbstractHereditary papillary renal carcinoma (HPRC) is a rare autosomal dominant disease characterized by the development of multiple papillary type I renal cell carcinomas. This hereditary kidney cancer form is caused by activating mutations in MET. Descriptions of patients with HPRC are scarce in the world literature, and no cases have been described in open sources in Russia. Here, we describe a 28-year-old female Russian patient with 7 and 10 primary papillary renal cell carcinomas in the left and right kidneys, respectively. The patient did not have a family history of any of the known hereditary cancer syndromes. A comprehensive medical examination was performed in 2016 including computed tomography and pathomorphological analysis. The observed tumors were resected in a two-step surgical treatment. In February 2019, no sign of disease progression was detected in follow-up medical examination. Molecular genetic analysis revealed the germline heterozygous missense variant in MET: c.3328G>A (p.V1110I; CM990852). We have discussed the biological effects of the detected mutation and the utility of DNA diagnostics for treating patients with HPRC.
AbstractTo the Editor. Our reports in 1994 and 1995 described families with an inherited predisposition for papillary renal carcinoma. Affected family members had a predisposition for multiple papillary tumors in both kidneys. Since those reports we have learned of several European families with papillary renal carcinoma.13 In addition, we evaluated 2 new families with papillary renal carcinoma, including 1 large family from Canada.4 It is clear that papillary renal carcinoma may occur in an inherited form, and that hereditary papillary renal carcinoma represents a distinct type of inherited cancer. A feature that characterizes these papillary renal carcinoma families is the long interval between detection of papillary renal earcinoma in an individual family member and referral of the family to a major cancer genetics center. In the family pedigree shown in the figure, papillary renal carcinoma was detected in the first member in 1971 and in the second member in 1984. The family was referred to the National Cancer Institute in 1995, at which point papillary renal carcinoma had developed in 5 family members. In the Canadian family papillary renal carcinoma was diagnosed initially in 1978.4 Other family members had papillary renal carcinoma in 1980, 1980, 1984, 1985, 1987, 1990, 1990 and 1995. von Hippel-Lindau disease was diagnosed incorrectly in 1990. The family was evaluated at the National Cancer Institute in 1995, after 9 members had been diagnosed with renal cancer. Recognition that papillary renal carcinoma occurs on an inherited basis should lead to identification of additional families with this disorder. Family identification will depend on determination of family history in patients with renal tumors and on the histological type of renal carcinoma. Any family in which 2 members have papillary renal carcinoma should be referred to a cancer genetics center for further study and evaluation. The techniques to isolate the gene responsible for clear cell renal carcinomas are being used to isolate the gene(s) responsible for papillary renal carcinoma.5 The success of this effort depends on identifying additional families with papillary renal carcinoma, and studying these families in detail to detect occult renal neoplasms in asymptomatic family members.
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.
