DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for undifferentiated pleomorphic sarcoma — screening already-approved drugs against its 47-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleUndifferentiated pleomorphic sarcoma maps to a 47-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 undifferentiated pleomorphic sarcoma 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
HRas proto-oncogene, GTPase (HRAS) — HRAS 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 gnpdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 8ELT · 1.66 Å · ligand PHOSPHOAMINOPHOSPHONIC ACID-GUANYLATE ESTER (GNP). Experimental structure, not a prediction.
What the evidence adds up to
A 2019 case report describes a 48-year-old woman with primary cardiac undifferentiated pleomorphic sarcoma who received cytoreductive surgery (incomplete resection) followed by seven cycles of doxorubicin and ifosfamide. Cardiovascular magnetic resonance showed a complete response, with only fibrosis visible and no detectable tumour. The patient remained free of recurrence 26 months from diagnosis, with no compromise of quality of life. The authors note that median survival for primary cardiac sarcoma is typically 6 to 12 months. A 2024 case report of a 35-year-old man with an unresectable UPS in the gluteal region, complicated by infection, describes the tumour as highly aggressive and notes that treatment typically involves surgical resection, with radiation or chemotherapy depending on size, location, and aggressiveness.
A 2019 case report of an 85-year-old man with a subcutaneous UPS on his back, who had prior prostate cancer and radiotherapy, emphasises that patients usually present late with advanced local disease or metastasis, most often to lungs and lymph nodes. Treatment is surgical with wide local excision; neoadjuvant or adjuvant radiotherapy has been advocated. A 2021 genomic analysis of a radiation-induced intracranial UPS in an 83-year-old woman found KIT and PDGFRA alterations, but states that clinical prognosis remains exceedingly poor despite maximal surgical resection and nonstandardised adjuvant therapy, and that there is a lack of genetic or molecular characterisation to guide targeted therapies.
A 2020 study of the extracellular matrix in rhabdomyosarcoma and the RMS/UPS continuum, using tissue microarrays of 48 murine and 4 human sarcomas, found increased expression of type XVIII collagen alpha 1 (COL18A1) in RMS, which was clinically associated with decreased long-term survival. It also identified increased RNA expression of COL4A1, FBN2, PLOD1, and PLOD2 in human RMS relative to normal skeletal muscle. The authors suggest these matrix components may be therapeutically targetable, but this work is preclinical and limited to correlative findings in small sample sets.
What is still missing are prospective trials that test whether the chemotherapy regimen that produced a complete response in one cardiac case can be replicated in a larger, defined UPS population. There is no validated molecular stratification for UPS, and the genomic characterisation of intracranial cases remains anecdotal. The extracellular matrix findings are from murine models and only four human sarcomas, with no clinical data on whether targeting COL18A1 or collagen-modifying enzymes improves survival. Funding for multi-centre trials, standardised adjuvant protocols, and prospective collection of genomic and outcome data are needed before any of these observations can change practice.
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.
International Journal of Molecular Sciences · 2022 · 4 citations · open access
Plocabulin, a Novel Tubulin Inhibitor, Has Potent Antitumour Activity in Patient-Derived Xenograft Models of Soft Tissue Sarcoma
AbstractA clinically relevant subset of patients with soft tissue sarcoma presents with either locally advanced or upfront metastatic disease, or will develop distant metastases over time, despite successful treatment of their primary tumour. The currently available systemic agents to treat such advanced cases only provide modest disease control and are not active in all histological subtypes. Thus, there is an unmet need for novel and more efficacious agents to improve the outcome of this rare disease. In the current preclinical in vivo study, we evaluated plocabulin, a novel tubulin inhibitor, in five distinct histological subtypes of soft tissue sarcoma: dedifferentiated liposarcoma, leiomyosarcoma, undifferentiated sarcoma, intimal sarcoma and CIC-rearranged sarcoma. The efficacy was tested in seven patient-derived xenograft models, which were generated by the engraftment of tumour fragments from patients directly into nude mice. The treatment lasted 22 days, and the efficacy of the drug was assessed and compared to the doxorubicin and vehicle groups by volumetric analysis, histopathology and immunohistochemistry. We observed tumour volume control in all the tested histological subtypes. Additionally, in three sarcoma subtypes, extensive central necrosis, associated with significant tumour regression, was seen. This histological response is explained by the drug’s vascular-disruptive properties, reflected by a decreased total vascular area in the xenografts. Our results demonstrate the in vivo efficacy of plocabulin in the preclinical models of soft tissue sarcoma and corroborate the findings of our previous study, which demonstrated similar vascular-disruptive effects in gastrointestinal stromal tumours—another subtype of soft tissue sarcoma. Our data provide a convincing rationale for further clinical exploration of plocabulin in soft tissue sarcomas.
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.
Research Square (Research Square) · 2020 · 1 citations · open access
Defining the Extracellular Matrix of Rhabdomyosarcoma
AbstractAbstract Background : Rhabdomyosarcoma (RMS) is the most common soft-tissue sarcoma of childhood with a propensity to metastasize. Current treatment for patients with RMS includes conventional systemic chemotherapy, radiation therapy and surgical resection; nevertheless, little to no improvement in long term survival has been achieved in decades – underlining the need for target discovery and new therapeutic approaches to targeting tumor cells or the tumor microenvironment. Methods : To evaluate cross-species sarcoma extracellular matrix production, we have used murine models which feature knowledge of the myogenic cell-of-origin. With focus on the RMS/undifferentiated pleomorphic sarcoma (UPS) continuum, we have constructed tissue microarrays of 48 murine and 4 human sarcomas to analyze expression of 7 different collagens, fibrillins and collagen-modifying proteins, with cross-correlation to RNA deep sequencing. Results : We have uncovered that RMS produces increased expression of type XVIII collagen alpha 1 (COL18A1), which is clinically associated with decreased long-term survival. We have also identified significantly increased RNA expression of COL4A1, FBN2, PLOD1 and PLOD2 in human RMS relative to normal skeletal muscle. Conclusion : These results complement recent studies investigating whether soft tissue sarcomas utilize collagens, fibrillins and collagen-modifying enzymes to alter the structural integrity of surrounding host extracellular matrix/collagen quaternary structure resulting in improved ability to improve the ability to invade regionally and metastasize, for which therapeutic targeting is possible.
Case Reports in Genetics · 2021 · 0 citations · open access
Genomic Characterization of Radiation-Induced Intracranial Undifferentiated Pleomorphic Sarcoma
AbstractIntracranial undifferentiated pleomorphic sarcoma remains a rare pathology within the sarcoma literature that may arise primarily or secondary after radiation therapy. Despite first-line treatment with maximal surgical resection, followed by nonstandardized adjuvant chemotherapy/radiation regimens, clinical prognosis remains exceedingly poor. Furthermore, there is a lack of genetic or molecular characterization to guide potential for targeted therapies. We present genomic analysis of a radiation-induced intracranial undifferentiated pleomorphic sarcoma in an 83-year-old woman with notable KIT and PDGFRA alterations. Further similar genomic studies of intracranial pleomorphic sarcoma are needed to develop better therapies for this rare but challenging disease entity.
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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