DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for epithelioid type angiomyolipoma — 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 moduleEpithelioid type angiomyolipoma 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
approvedSunitinibApproved drug
Structures already discussed alongside epithelioid type angiomyolipoma in the retrieved literature, rendered from public PubChem SMILES. Which drugs appear here reflects the evidence found, not a ranked prediction.
Molecular view
KIT kinase domain — Sunitinib has a real, experimentally solved structure in complex with this target (PDB 3G0E, 1.6 Å). This is the drug's own deposited structure, not a prediction, and confirms it is a structurally characterised molecule rather than an untested guess.
Loading structure…
helix sheet b49drag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 3G0E · 1.6 Å · ligand Sunitinib (B49). Experimental structure, not a prediction.
What the evidence adds up to
Epithelioid angiomyolipoma is an uncommon mesenchymal tumour with malignant potential, frequently associated with tuberous sclerosis complex. Histologically it is characterised by sheets or nests of large polygonal epithelioid cells with abundant eosinophilic or occasionally clear cytoplasm, often with prominent nucleoli, and may include multinucleated and markedly pleomorphic forms. Nearly all epithelioid angiomyolipomas show immunoreactivity for both melanocytic and myoid markers, and ultrastructurally they show evidence of melanogenesis by the presence of premelanosomes. The tumour can mimic a variety of intra-abdominal neoplasms including renal cell carcinoma, renal oncocytoma, adrenal cortical neoplasm, epithelioid smooth muscle tumour, epithelioid peripheral nerve sheath tumour, epithelioid gastrointestinal stromal tumour, epithelioid melanoma, hepatoblastoma, and hepatocellular carcinoma. In children, renal epithelioid angiomyolipoma appears to be the most common site, and in one review of 17 cases, 3 had metastasised to other organs.
Conventional cytotoxic agents have been reported to be disappointingly inactive against malignant epithelioid angiomyolipoma, and the prognosis of unresectable or recurrent disease is described as dismal. In a 2011 case report, a 52-year-old man with recurrent malignant epithelioid angiomyolipoma after nephrectomy was treated with everolimus at 10 mg per day. Computed tomographic scans after 2 months showed the tumours to be markedly decreased in size, and the patient had no signs of disease progression over 7 months as of February 2011. A 2015 case report describes a 12-year-old male with malignant epithelioid angiomyolipoma treated according to adult protocols including sunitinib, everolimus and axitinib; the authors concluded that adult protocols could be safely used in rare childhood malignancies, but no specific response or survival data are given for that child. A 2013 case report of a 7-year-old boy with epithelioid angiomyolipoma notes the tumour presented highly aggressive biobehaviour, but does not report treatment outcome.
A 2020 phase II trial of everolimus in sporadic (non-tuberous sclerosis) angiomyolipomas enrolled 20 patients with tumours 3 cm or larger. Patients received 10 mg everolimus daily for 4 planned 28-day cycles. Response was defined as a 25% or greater volumetric reduction. Of 18 evaluable patients, 10 (55.6%) exhibited a 25% or greater reduction at 4 months (median reduction 58.5%), and 10 of 14 (71.4%) at 6 months (median reduction 58.2%). However, 4 patients (20%) were withdrawn due to protocol-defined toxicities, and 8 (40%) self-withdrew due to side effects. Only 11 patients (55%) completed 4 cycles and 7 (35%) completed 6 cycles. This trial did not specifically enrol patients with the epithelioid variant, and the high rate of treatment discontinuation is notable.
What is still missing is prospective data specifically in malignant epithelioid angiomyolipoma, which is far rarer than classic angiomyolipoma. No randomised trial has been conducted in that subtype. The existing evidence rests on single case reports and a phase II trial in sporadic angiomyolipoma that did not stratify by histology. The toxicity of everolimus led to a high withdrawal rate even in that trial, and no data exist on whether the epithelioid variant responds differently from classic angiomyolipoma. Adequately powered trials would require multi-centre collaboration and likely years of accrual, and no such trial is registered.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
PubMed · 2011 · 57 citations
Epithelioid angiomyolipoma: a morphologically distinct variant that mimics a variety of intra-abdominal neoplasms.
AbstractThis review examines the histopathologic, immunohistochemical, ultrastructural, and molecular biologic features of epithelioid angiomyolipoma (EAML), with an emphasis on the differential diagnosis of intra-abdominal EAML. Epithelioid angiomyolipoma is an uncommon mesenchymal tumor with malignant potential, frequently associated with tuberous sclerosis complex. Histologically, EAML is characterized by sheets or nests of large polygonal epithelioid cells with abundant eosinophilic or occasionally clear cytoplasm, often with prominent nucleoli, and EAML may include multinucleated and markedly pleomorphic forms. As these tumors share a distinctive perivascular epithelioid cell phenotype, they belong to the PEComa tumor family. Nearly all EAMLs show immunoreactivity for both melanocytic and myoid markers. Ultrastructurally, EAMLs show evidence of melanogenesis by the presence of premelanosomes. Epithelioid angiomyolipoma can pose significant diagnostic challenges as it mimics morphologically a variety of neoplasms including renal cell carcinoma, renal oncocytoma, adrenal cortical neoplasm, epithelioid smooth muscle tumor, epithelioid peripheral nerve sheath tumor, epithelioid gastrointestinal stromal tumor, epithelioid melanoma, hepatoblastoma, and hepatocellular carcinoma. The variation in immunophenotype in these tumors requires a prudent use of immunohistochemistry, which may occasionally need complementation by electron microscopy to establish the correct diagnosis.
Japanese Journal of Clinical Oncology · 2011 · 50 citations
Dramatic Tumor Response to Everolimus for Malignant Epithelioid Angiomyolipoma
AbstractMalignant epithelioid variant of angiomyolipoma has aggressive characteristics, against which conventional cytotoxic agents have been reported to be disappointingly inactive, and the prognosis of unresectable or recurrent disease is dismal poor. A 52-year-old man with a history of left nephrectomy for epithelioid angiomyolipoma was referred to our institution. The computed tomographic scan showed a soft tissue dense mass around the Rex's recess and behind the spleen, and a large pelvic mass. Specimens obtained by percutaneous needle biopsy confirmed the recurrence of malignant epithelioid angiomyolipoma. Everolimus was initiated at 10 mg per day for recurrent disease. Computed tomographic scans 2 months later showed the tumors to be markedly decreased in size. The patient has continued with this treatment on an outpatient basis without signs of disease progression over 7 months, as of February 2011. In this case, treatment with everolimus resulted in dramatic tumor response for the malignant epithelioid variant of angiomyolipoma.
International Journal of Surgical Pathology · 2000 · 29 citations
Pleomorphic Angiomyolipoma of Digestive Tract: A Heretofore Unrecognized Entity
AbstractTwo cases of pleomorphic angiomyolipoma (AML) composed of bizarre epithelioid smooth muscle cells located in the gastrointestinal tract are reported. One involved the appendix of a 6-year-old girl, and the second the cecum of a 22-year-old woman. In both instances the tumor cells were immunoreactive for HMB-45 and A103. To the best of our knowledge, this peculiar variant of an AML has not previously been recognized in this location. Int J Surg Pathol 8(1):67-72, 2000
The Journal of Urology · 2020 · 15 citations · open access
Sporadic Angiomyolipomas Growth Kinetics While on Everolimus: Results of a Phase II Trial
AbstractPURPOSE: Everolimus decreases tumor volume of renal angiomyolipomas in patients with tuberous sclerosis. No prospective data are available regarding the effect of everolimus on the growth kinetics in patients with sporadic angiomyolipomas. We sought to determine the safety and efficacy of everolimus in the volumetric reduction of sporadic angiomyolipomas. MATERIALS AND METHODS: This multi-institutional, prospective, phase II trial, enrolled patients with 3 cm or larger sporadic angiomyolipomas who were candidates for surgical resection or percutaneous angioembolization. Patients received 10 mg everolimus daily for 4 planned 28-day cycles. Response was defined as a 25% or greater volumetric reduction of patient angiomyolipoma. Baseline, 4, 6 and 12-month volumetric analyses were performed using magnetic resonance imaging. Everolimus was discontinued in those with less than 25% volumetric reduction after 4 cycles. Those with 25% or greater volumetric reduction received 2 additional cycles. The primary outcomes were the efficacy of everolimus in the volumetric reduction of angiomyolipomas by 25% or more, and the safety and tolerability of everolimus. RESULTS: Overall 20 patients were enrolled at 5 centers. Of these patients 11 (55%) completed 4 cycles and 7 (35%) completed 6 cycles. Efficacy was demonstrated, with 10 of 18 (55.6%) patients exhibiting a 25% or greater reduction in tumor volume at 4 months (median 58.5%) and 10 of 14 (71.4%) patients exhibiting a 25% or greater reduction in tumor volume at 6 months (median 58.2%). Four (20%) patients were withdrawn due to protocol defined toxicities and 8 (40%) self-withdrew from the study due to side effects. CONCLUSIONS: Everolimus was effective in causing volumetric reduction of angiomyolipomas by 25% or greater in most patients but was associated with a high rate of treatment discontinuation.
Canadian Urological Association Journal · 2015 · 11 citations · open access
Malignant epitheloid angiomyolipoma of the kidney in a child treated with sunitinib, everolimus and axitinib
AbstractThe malignant variant of epithelioid angiomyolipoma (EAML) of the kidney is uncommon, extremely aggressive and behaves like a renal cell carcinoma. We present a case of a 12-year-old male with malignant EAML who was treated according to adult treatment protocols. To our knowledge, axitinib has not been used before in children. We conclude that adult protocols, in this rare case, could be safely used in rare childhood malignancies.
International Journal of Surgical Pathology · 2013 · 7 citations
Malignant Renal Angiomyolipoma With Metastases in a Child
AbstractThe biological character of epithelioid angiomyolipoma (EAML) remains controversial and little is known about EAML in children. We present a case of a 7-year-old boy with abdominal distention, diagnosed as EAML. Under microscopy, epithelioid cells were observed, with eosinophilic or slightly eosinophilic cytoplasm and nuclear pleomorphism, thick-walled blood vessels, and some cells that were differentiated to smooth muscle cells or fat cells were easily observed. Immunochemical staining showed that Melan-A and HMB45 were positive. The tumor presented highly aggressive biobehavior. Furthermore, we reviewed and analyzed cases of diagnosed EAML in our hospital and those reported in the literature. Renal EAML (10/17) was most common, and the EAML of 3 of 17 patients metastasized to other organs.
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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