DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for PTEN hamartoma tumor syndrome — 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 modulePTEN hamartoma tumor syndrome 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 pten hamartoma tumor syndrome 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
phosphatase and tensin homolog (PTEN) — PTEN 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…
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RCSB Protein Data Bank · entry 1D5R · 2.1 Å · ligand L(+)-TARTARIC ACID (TLA). Experimental structure, not a prediction.
What the evidence adds up to
In a retrospective review of 22 patients with PTEN hamartoma tumour syndrome (PHTS) aged 1 to 18 years (median 9), 4 had fast flow vascular anomalies. Over a median follow-up of 8 years (range 4–13), three of those four showed progressive increase in hamartoma size and development of new fast flow vascular anomalies. Surgical excision of a hamartoma in one patient led to recurrence within 3 months. Pain related to fast flow vascular anomalies responded well to embolisation; pain from PTEN hamartoma responded poorly to percutaneous sclerosant injection but improved with oral sirolimus. No correlation was found between serum sirolimus levels and the frequency or timing of recurrence of fast flow vascular anomalies or hamartomas. Complications included sclerosant migration into digital arteries (n=1), subclavian vein stenosis from glue migration (n=1), oral mucositis (n=4), and elevated triglycerides (n=4). The authors state that sirolimus improves quality of life but does not prevent disease progression.
A separate case report describes an adolescent with Cowden syndrome and recurrent life-threatening upper gastrointestinal bleeding from hamartomatous polyposis, in whom sirolimus was used to improve clinical symptoms. The authors note that sirolimus use is infrequently addressed in the paediatric literature for PTEN mutations. Another report of two patients in Singapore with de novo PTEN mutations and gastrointestinal polyposis of mixed histologies highlights that diagnosis was delayed despite high Cleveland Clinic scores, due to limited clinician awareness.
A 2025 commentary reports that somatic loss of PTEN through copy-neutral loss of heterozygosity and uniparental disomy in endothelial cells leads to vascular malformations in PHTS, and that these malformations respond to PI3K/AKT/mTOR pathway inhibitors. The same commentary notes that the genetic abnormalities underlying the phenotypic variation in PHTS remain poorly understood.
What is still missing are prospective trials with standardised dosing and monitoring of sirolimus or other PI3K/AKT/mTOR inhibitors in PHTS, particularly in children. The evidence rests on small retrospective series and single case reports. No randomised controlled trial has been conducted. Patient stratification by specific PTEN mutation type or by presence of somatic second hits is not yet incorporated into treatment decisions. Funding for multi-centre natural history studies and for trials that separate effects on vascular anomalies from effects on hamartoma growth 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.
Cancers · 2021 · 57 citations · open access
PTEN Hamartoma Tumor Syndrome/Cowden Syndrome: Genomics, Oncogenesis, and Imaging Review for Associated Lesions and Malignancy
AbstractPTEN hamartoma tumor syndrome/Cowden syndrome (CS) is a rare autosomal dominant syndrome containing a germline PTEN mutation that leads to the development of multisystem hamartomas and oncogenesis. Benign tumors such as Lhermitte–Duclos disease and malignant tumors involving the breast, thyroid, kidneys, and uterus are seen in CS. Radiologists have an integral role in the comanagement of CS patients. We present the associated imaging findings and imaging screening recommendations. Knowledge of the types of cancers commonly seen in CS and their imaging findings can aid in early tumor recognition during cancer screening to help ensure near-normal life spans in CS patients.
International Journal of Angiology · 2018 · 16 citations · open access
Temporal Evolution and Management of Fast Flow Vascular Anomalies in PTEN Hamartoma Tumor Syndrome
AbstractAbstract Phosphatase and tensin homolog (PTEN) hamartoma tumor syndrome (PHTS) is characterized by formation of recurrent benign tumors described as PTEN hamartoma of soft tissue that may contain fast flow vascular anomalies (FFVA). The purpose of this study is to review the temporal evolution and management of FFVA in PHTS. A retrospective review of 22 patients (9 males), age 1 to 18 (median 9) years diagnosed with PHTS at a tertiary care pediatric hospital between October 2002 and August 2017 revealed 4 patients with FFVA. Imaging, management, and treatment complications were reviewed. During median follow-up of 8 (range: 4–13) years, ultrasound and magnetic resonance imaging performed for recurrent pain, showed progressive increase in the size of hamartomas and development of new FFVA in three-fourth patients. Medical management included pain medications, oral sirolimus, and physical and psychiatric therapy. Surgical excision of hamartoma (n = 1) resulted in recurrence within 3 months. Between 4 and 24 (average 1.5/year) embolizations were performed per patient. Pain related to FFVA responded well to embolization. Pain secondary to PTEN hamartoma responded poorly to percutaneous sclerosant injection, but demonstrated improvement with sirolimus. There was no correlation between serum sirolimus levels and frequency/timing of recurrence of FFVA/hamartoma. Complications included sclerosant migration into digital arteries (n = 1), subclavian vein stenosis due to glue migration (n = 1), oral mucositis (n = 4), and elevated triglycerides (n = 4). Patients with PHTS present with recurrent pain requiring life-long management with a multi-disciplinary team. Pain due to FFVA responds to embolization, and pain due to hamartoma responds to sirolimus. This improves quality of life, but does not prevent disease progression.
The Turkish Journal of Pediatrics · 2022 · 7 citations · open access
Sirolimus treatment of a PTEN hamartoma tumor syndrome presenting with melena
AbstractBACKGROUND: PTEN hamartoma tumor syndrome (PHTS) is an umbrella term including Cowden syndrome (CS), Bannayan-Riley-Ruvalcaba syndrome (BRRS), PTEN-related Proteus syndrome (PS), and PTEN-related Proteus-like syndrome. One of the disorders in PHTS spectrum, CS is characterized by macrocephaly, mucocutaneous findings, gastrointestinal system (GIS) polyposis and an increased lifetime risk of GIS, breast, thyroid and other cancers. CASE: In this study, we report an adolescent patient presenting with recurrent life-threatening upper GIS bleeding as a result of hamartomatous polyposis. Genetic studies revealed a known pathogenic nonsense mutation confirming the initial diagnosis of CS. CONCLUSIONS: Additionally, we describe our therapeutic intervention to improve the patient`s clinical symptoms with sirolimus, which its use is infrequently addressed in the literature for pediatric age group harboring PTEN mutations.
The Open Pain Journal · 2023 · 2 citations · open access
Hindquarter Amputation as a Successful Treatment of Chronic Pain in an Adolescent with PTEN Hamartoma Tumor Syndrome
AbstractBackground: The PTEN hamartoma tumor syndrome comprises a group of rare conditions caused by germline mutations of the tumor suppressor gene PTEN (Phosphatase and TENsin homolog deleted on chromosome 10). They include Cowden syndrome, Lhermitte-Duclos disease, and Bannayan–Riley–Ruvalcaba syndrome, but it appears likely that these conditions represent the spectrum of PTEN hamartoma tumor syndrome, in which penetrance and clinical variability play significant roles. The clinical features of PTEN hamartoma tumor syndrome vary between individuals and can appear at any age. They include an increased risk for certain types of cancers and benign tumors, as well as tumor-like malformations (hamartomas) and neurodevelopmental disorders. Case Presentation: We report the case of an adolescent male with PTEN hamartoma tumor syndrome who developed severe chronic pain in the context of multiple arteriovenous malformations of the left lower limb. He successfully underwent hindquarter amputation to manage a nonhealing ulcer, recurrent episodes of life-threatening hemorrhage, and escalating analgesic requirements. He had a remarkable recovery with neither pain nor phantom sensory issues and significant improvement in his quality of life. Conclusion: Despite chronic preoperative pain, the radical surgery in this patient with PTEN hamartoma tumor syndrome resulted in an improved quality of life and virtually no long-term pain or analgesia requirements.
Hereditary Genetics · 2015 · 1 citations · open access
PTEN Hamartoma Tumour Syndrome:Gastrointestinal Manifestations ofTwo Cases Diagnosed in Singapore
AbstractPTEN hamartoma tumour syndrome is associated with germline mutations in the tumour suppressor gene, PTEN (phosphatase and tensin homolog gene), leading to formation of hamartomas due to unregulated cellular proliferation. Two patients presented with complications of hamartomas, which subsequently revealed multiple polyposis of mixed histologies throughout their gastrointestinal tracts. There was no family history for PTEN hamartoma tumour syndrome and both were eventually detected to have de novo PTEN mutations. Despite fulfilling diagnostic criteria and having high probabilities of a PTEN mutation (computed using PTEN Cleveland Clinic score), there was delayed diagnosis of PTEN hamartoma tumour syndrome due to limited awareness amongst treating clinicians. Thus PTEN hamartoma tumour syndrome should still be considered as a differential in patients with similar gastrointestinal manifestations for early diagnosis and intervention.
Lessons from the Oncology Clinic: Repurposing PI3K Pathway Inhibitors for the Treatment of PTEN Hamartoma Tumor Syndrome
AbstractThe underlying genetic abnormalities that cause the phenotypic variation seen in patients with PTEN hamartoma tumor syndrome (PHTS) are poorly understood. In this issue, Castillo and colleagues report that the somatic loss of PTEN through copy-neutral loss of heterozygosity and the resulting uniparental disomy in endothelial cells lead to vascular malformations in PHTS, which respond to PI3K/AKT/mTOR pathway inhibitors. See related article by Castillo et al., p. 1350 .
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.
