DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for leiomyoma — screening already-approved drugs against its 44-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleLeiomyoma maps to a 44-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
approvedProgesteroneApproved drug
Structures already discussed alongside leiomyoma in the retrieved literature, rendered from public PubChem SMILES. Which drugs appear here reflects the evidence found, not a ranked prediction.
Molecular view
Crystal structure of human 20alpha-HSD in ternary complex — Progesterone has a real, experimentally solved structure in complex with this target (PDB 1MRQ, 1.59 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 strdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 1MRQ · 1.59 Å · ligand Progesterone (STR). Experimental structure, not a prediction.
What the evidence adds up to
A 2022 case report describes a patient who had a hysterectomy for a large leiomyoma and was found to have pulmonary tumours seven and nine years later. The uterine tumour was re-confirmed as a cellular leiomyoma, while the lung tumours met diagnostic criteria for leiomyosarcoma. Whole-exome sequencing showed very similar mutational profiles across all three tumours, including a somatic homozygous deletion in the FH gene, a known driver in a rare subset of leiomyomas. The pulmonary tumours carried additional alterations in cancer-associated genes such as NRG1, MYOCD, and FGFR1. The authors conclude that this molecular evidence supports the occasional metastatic capability and malignant transformation of uterine leiomyomas, but note that further studies are needed to confirm whether FH-deficient or cellular histopathology tumours carry higher malignant potential.
A 2017 case report describes a 28-year-old woman with a perianal atypical leiomyoma, a benign tumour that can be difficult to distinguish from malignant smooth muscle tumours. The mass was resected completely, and the patient recovered uneventfully. The authors note that such tumours may undergo malignant changes and recommend complete resection with regular follow-up to avoid recurrence.
A 2019 study evaluated 12 patients who underwent surgery after high-intensity focused ultrasound (HIFU) for uterine leiomyoma. The median leiomyoma size before HIFU was 10.1 cm, decreasing to 8.75 cm after HIFU, then increasing to 9.1 cm before surgery. Surgery was planned due to increased tumour size (n=6), persistent symptoms (n=4), or newly developed lesions (n=2). The median interval between HIFU and surgery was 7 months. Histopathology showed infarction-type necrosis with granulation tissue and immune cell infiltration in all patients. The authors conclude that operative treatment should be considered in selected patients with tumours larger than 10 cm, multiple tumours, or persistent symptoms after HIFU.
What is still missing is prospective data on the true malignant potential of FH-deficient leiomyomas, larger studies on the long-term outcomes of HIFU versus surgery, and any randomised trial comparing HIFU with other treatments. Patient stratification by molecular subtype or tumour size remains unvalidated, and funding for such trials is 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.
Experimental and Molecular Pathology · 2022 · 14 citations · open access
Lung metastases and subsequent malignant transformation of a fumarate hydratase -deficient uterine leiomyoma
AbstractUterine leiomyomas, or fibroids, are very common smooth muscle tumors. Their potential to metastasize or transform into leiomyosarcomas is extremely low. Here, we report a patient who underwent hysterectomy due to a large leiomyoma and who was diagnosed with pulmonary tumors seven and nine years later. Histopathological re-evaluation confirmed the cellular leiomyoma diagnosis for the uterine tumor, whereas the pulmonary tumors met the diagnostic criteria of a leiomyosarcoma. Whole-exome sequencing revealed very similar mutational profiles in all three tumors, including a somatic homozygous deletion in a rare, but well-established leiomyoma driver gene FH. Tumor evolution analysis confirmed the clonal origin of all three tumors. In addition to mutations shared by all three tumors, pulmonary tumors harbored additional alterations affecting e.g. the cancer-associated genes NRG1 and MYOCD. The second pulmonary leiomyosarcoma harbored additional changes, including a mutation in FGFR1. In global gene expression profiling, the uterine tumor showed similar expression patterns as other FH-deficient leiomyomas. Taken together, this comprehensive molecular data supports the occasional metastatic capability and malignant transformation of uterine leiomyomas. Further studies are required to confirm whether FH-deficient tumors and/or tumors with cellular histopathology have higher malignant potential than other uterine leiomyomas.
BioMed Research International · 2017 · 14 citations · open access
The Rising Phoenix-Progesterone as the Main Target of the Medical Therapy for Leiomyoma
AbstractLeiomyomas, also known as uterine fibroids, are a common benign tumor in women of reproductive age. These lesions disrupt the function of the uterus causing menorrhagia and pelvic pressure as well as reproductive disorders. These women pose a true challenge for clinicians in the attempt of choosing the suitable treatment for each patient. Patient's age, interest in fertility preservation, and leiomyoma location and size are all factors to be taken into account when deciding upon the preferable therapeutic option. For the past few decades, surgical treatment was the only reliable long-term treatment available. A variety of surgical approaches have been developed over the years but these developments have come at the expense of other treatment options. The classical medical treatment includes gonadotropin-releasing hormone (GnRH) agonists and antagonists. These agents are well known for their limited clinical effect as well as their broad spectrum of side effects, inspiring a need for new pharmacological treatments. In recent years, promising results have been reported with the use of selective progesterone receptor modulators (SPRM). Long-term clinical trials have shown a reduction in bleeding and shrinkage of leiomyoma mass. These results instill hope for women suffering from symptomatic leiomyomas seeking an effective, long-term medical option for their condition.
AbstractRATIONALE: Reports on perianal atypical leiomyoma, a perianal tumor, are rare. We confirmed a perianal atypical leiomyoma by its clinical presentation, magnetic resonance imaging findings, and immunohistochemistry. PATIENT CONCERNS: A 28-year-old female with a perianal mass found more than 4 years ago. The 5cm_4cm_4cm sized mass was located on the left side of the anus and vagina; The magnetic resonance imaging (MRI) scan revealed: A 4.1cm × 5.2cm × 4.9cm sized round mass was observed on the left side of the circumference. DIAGNOSES: Perianal atypical leiomyoma. INTERVENTIONS: anal peripheral mass resection was performed under lumbar anesthesia. OUTCOMES: The postoperative course was uneventful, healing, the patient was discharged. LESSONS: Perianal atypical leiomyomas are benign tumors, but with the clinically atypical leiomyoma, it is sometimes difficult to distinguish between potential malignant smooth muscle tumors,and there may be malignant changes. Surgery should ensure complete resection, and to avoid postoperative recurrence, there should be a regular follow-up.
Clinical characteristics of patients with leiomyoma who undergo surgery after high intensity focused ultrasound (HIFU)
AbstractOBJECTIVE: We evaluated the clinical characteristics of patients who underwent surgery after high intensity focused ultrasound (HIFU) to treat uterine leiomyoma. METHODS: From June 2016 to September 2017, patients at our hospital who underwent HIFU to treat uterine leiomyoma prior to surgery were enrolled. All patients underwent pelvic magnetic resonance imaging (MRI) before and after HIFU. If 6 months had passed since the last pelvic MRI was performed, imaging was performed again before the operation. RESULTS: . The median size of the leiomyoma was 10.1 (range, 7.8-14.0) cm before HIFU, which changed to 8.75 (range, 5.9-14.8) cm after HIFU. The median size increased to 9.1 (range, 5.9-18.0) cm before the operation. Surgery was planned for several reasons, including an increase in the leiomyoma size (n=6), persistent symptoms (n=4), and newly developed lesion (n=2). The median interval between HIFU and surgery was 7 (range, 3-32) months. Ten of the 12 patients underwent laparoscopic surgery, while the others underwent laparotomy; 6 patients also underwent laparoscopic myomectomy, and 4 underwent hysterectomy. Histopathologic findings showed infarction-type necrosis surrounded by granulation tissue with the infiltration of lymphocytes and macrophages in all patients. CONCLUSION: Treatment of leiomyoma with operative procedures should be considered in selected patients with tumor size greater than 10 cm, multiple tumors, and persistent symptoms after HIFU treatment.
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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