DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for Tenosynovial Giant Cell Tumor — screening already-approved drugs against its 4-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleTenosynovial Giant Cell Tumor maps to a 4-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 tenosynovial giant cell tumor 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
colony stimulating factor 1 receptor (CSF1R) — CSF1R 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 ukidrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 8JOT · 1.69 Å · ligand Sulfatinib (UKI). Experimental structure, not a prediction.
What the evidence adds up to
In a phase 1 trial of the CSF1R inhibitor PLX3397 (later named pexidartinib), 23 patients with tenosynovial giant cell tumour were enrolled in the extension cohort. Twelve had a partial response and seven had stable disease; responses usually appeared within the first four months and the median duration exceeded eight months. The most common adverse events were fatigue, hair colour change, nausea, dysgeusia, and periorbital oedema; discontinuation due to side effects was rare. The same drug, pexidartinib, received FDA approval in August 2019 for symptomatic tenosynovial giant cell tumour with severe morbidity or functional limitations not amenable to surgery. It is an oral tyrosine kinase inhibitor that selectively blocks CSF1 receptor. Clinicians are warned to monitor for liver-related adverse events that may require dose adjustment or stopping treatment.
A 2026 review of diffuse tenosynovial giant cell tumour reports that arthroscopic or open synovectomy can have recurrence rates exceeding 50%. CSF1 receptor inhibitors produce symptom palliation and tumour burden reduction in approximately 40% of patients. The review suggests these drugs may also be used in a neoadjuvant setting to downstage surgery, but notes that further research is needed to define the role of systemic agents and to develop multidisciplinary protocols. A separate 2025 review states that drug therapy and active surveillance have become important options for unresectable or high-recurrence-risk disease, and that imaging and patient-reported outcome tools are crucial for evaluating efficacy.
A 2021 case report describes an intramuscular localised tenosynovial giant cell tumour with a novel CSF1-CD96 fusion transcript, expanding the known molecular profile beyond the most common COL6A3 partner. A 2015 study confirmed that CSF1 expression is elevated in most tenosynovial giant cell tumours and that the pattern is consistent with the pathological features of the disease. What remains missing are prospective trials comparing neoadjuvant CSF1R inhibition plus surgery versus surgery alone, long-term safety data beyond the initial trials, and validated patient stratification tools to predict which tumours will respond to systemic therapy versus those that can be safely observed.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
New England Journal of Medicine · 2015 · 582 citations
Structure-Guided Blockade of CSF1R Kinase in Tenosynovial Giant-Cell Tumor
AbstractBACKGROUND: Expression of the colony-stimulating factor 1 (CSF1) gene is elevated in most tenosynovial giant-cell tumors. This observation has led to the discovery and clinical development of therapy targeting the CSF1 receptor (CSF1R). METHODS: Using x-ray co-crystallography to guide our drug-discovery research, we generated a potent, selective CSF1R inhibitor, PLX3397, that traps the kinase in the autoinhibited conformation. We then conducted a multicenter, phase 1 trial in two parts to analyze this compound. In the first part, we evaluated escalations in the dose of PLX3397 that was administered orally in patients with solid tumors (dose-escalation study). In the second part, we evaluated PLX3397 at the chosen phase 2 dose in an extension cohort of patients with tenosynovial giant-cell tumors (extension study). Pharmacokinetic and tumor responses in the enrolled patients were assessed, and CSF1 in situ hybridization was performed to confirm the mechanism of action of PLX3397 and that the pattern of CSF1 expression was consistent with the pathological features of tenosynovial giant-cell tumor. RESULTS: A total of 41 patients were enrolled in the dose-escalation study, and an additional 23 patients were enrolled in the extension study. The chosen phase 2 dose of PLX3397 was 1000 mg per day. In the extension study, 12 patients with tenosynovial giant-cell tumors had a partial response and 7 patients had stable disease. Responses usually occurred within the first 4 months of treatment, and the median duration of response exceeded 8 months. The most common adverse events included fatigue, change in hair color, nausea, dysgeusia, and periorbital edema; adverse events rarely led to discontinuation of treatment. CONCLUSIONS: Treatment of tenosynovial giant-cell tumors with PLX3397 resulted in a prolonged regression in tumor volume in most patients. (Funded by Plexxikon; ClinicalTrials.gov number, NCT01004861.).
Pexidartinib (TURALIO™): The First FDA-Indicated Systemic Treatment for Tenosynovial Giant Cell Tumor
AbstractTenosynovial giant cell tumor is a rare proliferative tumor that arises from the synovium, bursae, or tendon sheaths due to an overproduction of colony-stimulating factor 1. Historically, treatment options for patients with local or diffuse tenosynovial giant cell tumor have been limited to surgical interventions. However, for some patients, surgical resection could worsen functional limitations and/or morbidity. In August 2019, the FDA approved pexidartinib (TURALIO™, Daiichi Sankyo), the first systemic treatment option for adult patients with symptomatic tenosynovial giant cell tumor associated with severe morbidity or functional limitations that were not amenable to improvement with surgery. Pexidartinib is an oral tyrosine kinase inhibitor with selective inhibition of colony-stimulating factor 1 receptor and is the first systemic therapy to show significant improvement in overall response rates when compared with placebo. Clinicians using pexidartinib should monitor for liver-related adverse events, which may require treatment interruption, dose reduction, or treatment discontinuation. Pexidartinib provides a novel non-surgical treatment option for patients with tenosynovial giant cell tumor that may significantly improve patients' overall response, range of motion, physical function, tumor volume, and stiffness.
Journal of the American Academy of Orthopaedic Surgeons · 2025 · 6 citations
Tenosynovial Giant Cell Tumor and Pigmented Villonodular Synovitis
AbstractTenosynovial giant cell tumors (TGCTs) are a spectrum of benign growths that can occur in both intra-articular and extra-articular locations. The pattern of involvement also varies from nodular, typically small-volume disease to extensive and diffuse synovial infiltration. Surgical resection remains the treatment of choice for most patients and resection techniques include arthroscopic, open, or a combined approach. However, TGCT can be locally aggressive and exhibit high recurrence rates even after adequate surgical removal. Improved understanding of the complex genetic and environmental factors that lead to these proliferative disorders have modernized treatment options. Discovery of the unique role that tumor cell expression of the colony-stimulating-factor1 and propagation of the inflammatory cascade has led to the use of adjuvant medications to improve outcomes. In-depth knowledge of the etiology, clinical presentation, diagnosis, workup, historical treatments, and new treatment options for patients with TGCT are crucial for orthopaedic surgeons to understand and work effectively with a multidisciplinary treatment team.
AbstractTenosynovial giant cell tumors typically arise in the synovium of joints, bursae, or tendon sheaths. They may occur in an intra- or extra-articular location and can be divided into localized and diffuse types. The neoplastic nature of the lesion has been supported by a recurrent CSF1 gene rearrangement in a small subset of lesional cells, of which the most common fusion partner is COL6A3. Herein, we report a case of intramuscular localized tenosynovial giant cell tumor harboring a novel CSF1-CD96 fusion transcript, thus expanding the molecular profile of this tumor.
JBJS Open Access · 2026 · 1 citations · open access
Current Treatment Strategies for Diffuse Tenosynovial Giant Cell Tumor: A Review of the Literature
AbstractBackground: Diffuse tenosynovial giant cell tumor (DTGCT) is a locally aggressive benign tumor of the synovium. Patients often initially present with pain, stiffness, and swelling of the affected joint with varying levels of severity. Treatment traditionally involved surgical resection exclusively; however, this could be complicated by high disease recurrence rates. New research has introduced several targeted systemic therapies onto the market changing the treatment paradigm and necessitating a multidisciplinary treatment approach in specialized centers to optimize patient outcomes. Methods: This review synthesizes the current literature on DTGCT including its pathophysiology, classification, diagnosis, and available treatment options. There is a particular focus on the newer systemic therapies available and how these medications may be used in conjunction with surgery to enhance disease control. Results: DTGCT most commonly affects young to middle-aged adults, with a slight female predominance, and is most frequently found in the knee. Arthroscopic and even open synovectomy can have disease recurrence rates exceeding 50%. Colony stimulating factor 1 (CSF1) receptor inhibitors have proven effective at symptom palliation and reducing tumor burden in approximately 40% of patients. While these medications improve the quality of life for patients with unresectable disease, they may also be effective in the neoadjuvant setting to downstage surgical approaches and possibly improve disease control in otherwise highly morbid cases. Conclusions: Surgery alone, the traditional standard for DTGCT, is often insufficient due to high recurrence rates. Systemic therapies can restore function and improve quality of life in patients with advanced disease with rare-but potentially serious-adverse effects. Combining surgical resection with neoadjuvant CSF1R inhibition may provide superior outcomes. Further research is needed to refine the role of systemic agents and develop multidisciplinary protocols. Although initial symptoms often lead patients to community providers, optimal care for patients with DTGCT is best delivered at referral centers with dedicated musculoskeletal oncology programs. Level of Evidence: Level V. See Instructions for Authors for a complete description of levels of evidence.
DOAJ (DOAJ: Directory of Open Access Journals) · 2025 · 0 citations · open access
Treatment Choices for Tenosynovial Giant Cell Tumor: Surgery or Observation?
AbstractTenosynovial giant cell tumor (TGCT) is a rare mesenchymal tumor that clinically presents as nodular-type or diffuse-type (D-TGCT). D-TGCT is more aggressive, has a higher surgical recurrence rate, and can potentially lead to severe joint destruction. The traditional treatment is primarily through surgical intervention. Recent advancements in understanding the molecular mechanisms of the disease and the development of new drugs have significantly changed TGCT treatment strategies. Drug therapy and active surveillance have become important treatment options for unresectable or high-recurrence-risk TGCT. Imaging examinations and patient-reported outcome tools play a crucial role in evaluating efficacy and guiding treatment decisions. Comprehensive management by a multidisciplinary team and utilizing individualized treatment plans can significantly improve the quality of life and treatment outcomes of patients. Future research should explore the molecular mechanisms of TGCT, enhance multidisciplinary collaboration, and emphasize long-term management to improve treatment efficacy and patient prognosis.
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.
