DeCure for Undifferentiated high grade pleomorphic sarcoma of bone
DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for undifferentiated high grade pleomorphic sarcoma of bone — screening already-approved drugs against its 6-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleUndifferentiated high grade pleomorphic sarcoma of bone maps to a 6-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
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Peer review & paperComing soon
Peer-reviewed paper published open-access (preprint + journal).proof: DOI + open-access link + on-chain hash
Current lead
approvedRegorafenibApproved drug
Structures already discussed alongside undifferentiated high grade pleomorphic sarcoma of bone in the retrieved literature, rendered from public PubChem SMILES. Which drugs appear here reflects the evidence found, not a ranked prediction.
Molecular view
KRas proto-oncogene, GTPase (KRAS) — KRAS is one of the genes in this disease's Open Targets module — part of the target space DeCure's repurposing candidates point at. The protein backbone is drawn as a cartoon. The structure has phosphoaminophosphonic acid-guanylate ester bound in it, shown as sticks.
Loading structure…
helix sheet gnpdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 7VVB · 1.7 Å · ligand PHOSPHOAMINOPHOSPHONIC ACID-GUANYLATE ESTER (GNP). Experimental structure, not a prediction.
What the evidence adds up to
A 48-year-old woman with primary cardiac undifferentiated pleomorphic sarcoma, where complete resection was not possible, received seven cycles of doxorubicin and ifosfamide after cytoreductive surgery. Cardiovascular magnetic resonance showed a complete response with only fibrosis visible. She remained free of recurrence 26 months from diagnosis, with no compromise of quality of life. The authors note that standard chemotherapy with cytoreductive surgery can produce complete response and unusual long-term survival in this setting. No other patient in the provided abstracts achieved such an outcome.
A population-based cohort study from Japan examined 247 patients with primary undifferentiated pleomorphic sarcoma of bone. The 5-year disease-specific survival was 47.4% for the entire cohort, 56.4% for patients without metastasis at presentation (M0), and 16.9% for those with metastasis (M1). Metastasis on initial presentation and age 65 years or older were poor prognostic factors. Among 132 patients with localised, resectable tumours, adjuvant chemotherapy was associated with a hazard ratio of 0.43 for disease-specific survival and a 5-year disease-specific survival of 78.8% compared with 51.8% without adjuvant chemotherapy. The benefit was significant for tumours smaller than 8 cm (5-year survival 100% vs 54.6%) but not for tumours 8 cm or larger (68.7% vs 42%, P = 0.09). After propensity score matching, the association between adjuvant chemotherapy and improved disease-specific survival remained significant.
Two case reports describe presentations without long-term follow-up data. An 85-year-old man with a history of prostate cancer and radiotherapy had a subcutaneous undifferentiated pleomorphic sarcoma on his back; the authors note that patients usually present late with advanced local disease or metastasis, and treatment is surgical with wide local excision, with neoadjuvant or adjuvant radiotherapy advocated. A 35-year-old man presented with a growing mass in the gluteal region complicated by local and systemic infection; the tumour was unresectable, and the authors describe the case as devastating.
What is missing is a prospective randomised trial of adjuvant chemotherapy specifically for undifferentiated pleomorphic sarcoma of bone, with stratification by tumour size and surgical margin status. The Japanese cohort study is retrospective and registry-based; its propensity-score matching cannot eliminate unmeasured confounding. No data are available on the efficacy of any targeted therapy or immunotherapy for this sarcoma. Funding for a multicentre trial that could confirm or refute the survival benefit seen in the registry data has not been reported.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
BMC Cancer · 2019 · 20 citations · open access
Multidisciplinary approach to rare primary cardiac sarcoma: a case report and review
AbstractBACKGROUND: Undifferentiated pleomorphic sarcoma is a very rare and aggressive type of primary cardiac tumors. Most cardiac sarcomas result in rapid growth and quick death. According to different sources the median survival is typically 6 to 12 months. We are presenting a case of primary cardiac sarcoma with 26 months disease free survival following cytoreductive surgery and chemotherapy. CASE PRESENTATION: A 48-year-old woman with progressing symptoms of dyspnea and palpitations for over 2 months was referred to a cardiologist. With the help of echocardiography and cardiovascular magnetic resonance cardiac sarcoma was suspected. Open biopsy and cytoreductive surgery were performed, complete resection of the tumor was not possible. Histology revealed undifferentiated pleomorphic sarcoma. Seven cycles of chemotherapy with Doxorubicine and Ifosfamide were completed. Cardiovascular magnetic resonance revealed a complete response - only signs of fibrosis without any signs of tumor were visible. Follow ups with echocardiography, cardiovascular magnetic resonance and chest, abdomen and pelvic computed tomography is performed every 3 months. Twenty-six months from initial diagnosis the patient is still free of recurrence of tumor with no compromises of the quality of life. CONCLUSION: Standard chemotherapy together with cytoreductive surgery can have a complete response effect in undifferentiated pleomorphic sarcoma with unusual long-term survival.
International Journal of Surgery Case Reports · 2019 · 11 citations · open access
Malignant fibrous histiocytoma, now referred to as Undifferentiated Pleomorphic Sarcoma
AbstractINTRODUCTION: An 85year old male presented to his General Practitioner with a vague history of a lump on his back that was mobile and non tender. He had a previous history of advanced prostate cancer and radiotherapy treatment. PRESENTATION: We present an unexpected diagnosis of malignant fibrous histiocytoma of a subcutaneous lesion removed from the patient's back. DISCUSSION: Excisions of subcutaneous lesions along with cutaneous lesions form the majority of cases on a usual minor operations list. All lesions are sent for histopathological analysis and most are confirmed benign sebaceous cysts or lipomas. However the entity of malignant fibrous histiocytoma, now referred to as undifferentiated pleomorphic sarcoma (UPS) should be kept in mind. Patients will usually present late with advanced local disease or metastasis, usually to lungs and lymph nodes. Treatment is surgical with wide local excision and neoadjuvant/adjuvant radiotherapy has been advocated as well. CONCLUSION: Undifferentiated pleomorphic sarcoma should be a differential in subcutaneous lesions in older adults with a previous history of malignancy, radiation therapy and a mass in the subcutaneous tissue of the back.
Japanese Journal of Clinical Oncology · 2022 · 6 citations
Clinical characteristics of undifferentiated pleomorphic sarcoma of bone and the impact of adjuvant chemotherapy on the affected patients: a population-based cohort study
AbstractBACKGROUND: Clinical characteristics of undifferentiated pleomorphic sarcoma of bone are not elucidated. Herein, we clarify its clinical features and analyze the efficacy of adjuvant chemotherapy in patients with undifferentiated pleomorphic sarcoma of bone. METHODS: Prognostic factors and estimated disease-specific survival in 247 patients with primary undifferentiated pleomorphic sarcoma of bone were identified from a registry in Japan. The effect of adjuvant chemotherapy was evaluated in localized resectable cases, and the characteristics of the two groups treated with or without chemotherapy were adjusted using propensity score matching. RESULTS: The 5-year disease-specific survival rates were 47.4% in the entire cohort and 56.4 and 16.9% in the M0 and M1 groups, respectively. Multivariate disease-specific survival analysis revealed that metastasis on initial presentation and age ≥ 65 years were poor prognostic factors. Overall, 132 localized and resectable primary lesions were extracted. Adjuvant chemotherapy administration was a favorable prognostic factor (hazard ratio: 0.43, P = 0.04), and it significantly prolonged disease-specific survival compared with no adjuvant chemotherapy (5-year disease-specific survival: 78.8% vs. 51.8%, P = 0.008). Adjuvant chemotherapy prolonged disease-specific survival in patients with tumor size <8 cm (5-year disease-specific survival: 100% vs. 54.6%, P = 0.02); however, its efficacy decreased in those with tumor size ≥8 cm (5-year disease-specific survival: 68.7% vs. 42%, P = 0.09). After propensity score matching, adjuvant chemotherapy was significantly associated with good disease-specific survival (P = 0.02). CONCLUSIONS: Metastasis in the initial presentation was the poorest prognostic factor. On evaluating localized and resectable cases only, adjuvant chemotherapy significantly improved disease-specific survival, although its effect decreased in cases with large tumors.
International Journal of Surgery Case Reports · 2024 · 1 citations · open access
The devastating impact of unresectable infectious undifferentiated pleomorphic sarcoma in the gluteal region: A case report
AbstractINTRODUCTION AND IMPORTANCE: Undifferentiated pleomorphic sarcoma (UPS), previously known as malignant fibrous histiocytoma (MFH), is a highly aggressive soft tissue sarcoma characterized by its pleomorphic histology and lack of differentiation. CASE PRESENTATION: A 35-year-old man visited our oncology department with a complaint of a growing mass in his left buttock area. The mass had been increasing in size for the past six months, affected by local and systemic infection. While it was initially painless, the patient started feeling discomfort during sitting and physical activities a few weeks, but later the complication of tumor became more aggressive. CLINICAL DISCUSSION: UPS can arise in various anatomical sites, including the extremities, trunk, retroperitoneum, and head and neck region. Clinically, UPS may present as a rapidly growing mass, often with pain and limited range of motion. However, the presentation may vary depending on the site of origin. Treatment for UPS typically involves surgical resection, aiming to remove the tumor completely. Depending on the size, location, and aggressiveness of the tumor, additional treatments such as radiation therapy or chemotherapy may be recommended. CONCLUSION: Undifferentiated pleomorphic sarcoma (UPS) represents a rare and aggressive soft tissue sarcoma requiring prompt and accurate diagnosis for appropriate management. With its non-specific clinical presentation and histological features, UPS can be challenging to differentiate from other soft tissue tumors.
A Systematic Review and Meta-Analysis of Regorafenib's Effectiveness and Safety in the Treatment of Bone Sarcoma.
AbstractObjectives: Bone sarcomas are rare, aggressive tumors with poor outcomes and limited systemic options in advanced stages. This systematic review and meta-analysis evaluated its efficacy and safety in bone sarcomas using randomized controlled trials (RCTs). Methods: We searched PubMed, Scopus, and Web of Science for RCTs published from September 27, 2012, to October 14, 2024. After removing duplicates, 350 records were screened, and five RCTs met the inclusion criteria. Primary outcomes were progression-free survival (PFS), overall survival (OS), and adverse events (AEs). Study quality was assessed using the Cochrane Risk of Bias 2 (RoB2) tool. Meta-analyses were performed with a random-effects model, and heterogeneity was evaluated using I² statistics. All analyses were conducted using R version 4.3.1. Results: A total of 350 records were screened after duplicate removal, of which 339 were excluded based on title and abstract. Eleven full-text articles were assessed for eligibility, and six were excluded for not meeting RCT criteria, resulting in five RCTs being included. Most had metastatic disease at baseline. Regorafenib significantly improved PFS (MD = 9.69 weeks; 95% CI: 4.54-14.84; I² = 0%), with no statistically significant overall survival (OS) benefit (MD = 0.85 weeks; 95% CI: -36.33 to 38.02; I² = 0%). These findings were consistent across studies and histological subtypes. All pooled analyses demonstrated zero or near-zero heterogeneity (I² = 0%), indicating highly consistent treatment effects among trials. No significant between-group heterogeneity was observed in subgroup analyses, confirming that regorafenib's benefit on progression-free survival was stable across different bone sarcoma types. Common regorafenib-related AEs included hand-foot skin reaction, hypertension, fatigue, and diarrhea. Grade 3-5 events were mostly hypertension and pain, generally manageable with dose modifications. Safety results were also consistent across studies, showing zero or near-zero heterogeneity (I² = 0%) and no significant subgroup differences, indicating a homogeneous safety profile across sarcoma subtypes. Conclusion: Regorafenib significantly improves progression-free survival in bone sarcomas across multiple subtypes, with a manageable toxicity profile. These results support its use as a novel therapy and highlight the need for future trials focused on optimizing dosing and patient selection. .
Undifferentiated Pleomorphic Sarcoma of the Distal Thigh: A Case Report
AbstractThe undifferentiated pleomorphic sarcoma (UPS) is a rare malignant tumor of mesenchymal origin. Poorly differentiated tumor cells, which might take the form of giant cells, histiocytes, or spindle-shaped cells, make up the UPS variant of sarcomas. If soft tissue tumors enlarge and turn malignant, they may become an issue. Sarcoma is diagnosed by several tests, such as a physical examination, MRI, CT scan, or ultrasound. A biopsy yields information regarding the grade and subtype of the sarcoma and is required for a clear diagnosis. Chemotherapy, radiation therapy, and broad-margin excision are the standard treatments for cancers of the bone. UPS often appears in people between 50 and 70 years old. Yet, here we report a 40-year-old male diagnosed with UPS. Our goal is to discuss how unique our case is in comparison to others, as well as the available diagnostic and therapeutic alternatives in such cases.
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.
