DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for myxofibrosarcoma — screening already-approved drugs against its 31-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleMyxofibrosarcoma maps to a 31-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 myxofibrosarcoma 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
MDM4 regulator of p53 (MDM4) — MDM4 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 3~{s}drag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 6Q9Y · 1.2 Å · ligand 7-methoxy-~{N}-[(3~{S})-1-(4-methylphenyl)pyrrolidin-3-yl]-1~{H}-indole-3-carboxamide (HRQ). Experimental structure, not a prediction.
What the evidence adds up to
A retrospective analysis of 100 patients treated at a single Japanese cancer centre between 1999 and 2008 found that the estimated 5-year recurrence-free survival rate for myxofibrosarcoma was 74.8%. A histologically positive margin after surgery occurred in 28% of cases. On univariate analysis, primary unplanned resection at another facility and a histologically positive margin were significant predictors of local recurrence. On multivariate analysis, only primary unplanned resection at another facility remained significantly correlated with recurrence-free survival. The authors concluded that accurate diagnosis and adequate initial surgery are the most important factors for improving outcomes.
A low-grade myxofibrosarcoma on the forearm of a 44-year-old woman was completely resected. Although the tumour was remarkably hypocellular with only mild atypia, it had rapidly invaded into the underlying brachioradial muscle. This case demonstrates that even histologically low-grade myxofibrosarcoma can invade deep tissues. Orbital myxofibrosarcoma has been reported only five times in the literature; typical management is surgical excision with or without postoperative radiotherapy. Low-grade tumours rarely metastasise but have a high rate of local recurrence, and each recurrence increases metastatic risk.
A novel myxofibrosarcoma cell line, MUG-Myx1, was established from a primary tumour. The cell line showed gains and amplifications at chromosomal regions known to harbour tumour-associated genes including TIF, BRAF, MLL3, SMO, and MET, and loss of heterozygosity on chromosome 5q21. A stem-like cell population with high aldehyde dehydrogenase 1 activity was isolated from the cell line. These ALDH1high cells showed upregulation of the ABC transporters ABCB1 and ABCG2, higher expression of c-Myc, E-cadherin and SOX-2, and higher tumourigenicity and proliferation in NOD/SCID mice. The overall 5-year survival rate for myxofibrosarcoma is 60–70%.
No drug treatment is mentioned in any of these abstracts. What is missing is any prospective trial testing a systemic therapy, any validated biomarker to stratify patients by recurrence risk beyond surgical margin status, and any financial or organisational commitment to move from cell-line characterisation to clinical intervention.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Japanese Journal of Clinical Oncology · 2013 · 61 citations
An Analysis of Factors Related to Recurrence of Myxofibrosarcoma
AbstractOBJECTIVE: Myxofibrosarcoma is clinically characterized by a high frequency of local recurrence after surgery. To improve the clinical outcome of patients with myxofibrosarcoma, it is imperative to control any postsurgical local recurrence. METHODS: In this study, we performed a retrospective clinicopathologic analysis of 100 consecutive patients with myxofibrosarcoma to identify factors related to poor prognosis. All of the patients had been diagnosed, and had undergone surgery at the National Cancer Center Hospital between 1999 and 2008. RESULTS: At the initial visit to our hospital, 64 patients had primary myxofibrosarcoma, whereas 36 had undergone primary unplanned resection at other facilities. Of the 36 patients, 11 consulted our hospital before recurrence and 25 did so after recurrence. A histologically positive margin after surgery was evident in 28% of the cases overall. The estimated 5-year recurrence-free survival rate was 74.8%. Univariate analysis showed that primary unplanned resection at another facility (P = 0.0001) and a histologically positive margin (P = 0.0224) were significant predictors of local recurrence. When these two factors were subjected to multivariate analysis, only primary unplanned resection at another facility was significantly correlated with the estimated recurrence-free survival rate (P = 0.0011). Primary unplanned resection was also significantly related to the 5-year disease-free survival rate (P = 0.0401). CONCLUSIONS: Our findings indicate that primary unplanned resection at a non-referral hospital is the most important risk factor related to poor prognosis of myxofibrosarcoma. Accurate diagnosis and adequate initial surgery are most important factors for improving the clinical outcomes of myxofibrosarcoma.
The novel myxofibrosarcoma cell line MUG-Myx1 expresses a tumourigenic stem-like cell population with high aldehyde dehydrogenase 1 activity
AbstractBACKGROUND: Myxofibrosarcoma comprises a spectrum of malignant neoplasms withprominent myxoid stromata, cellular pleomorphism, and distinct curvilinear vascular patterns. These neoplasms mainly affect patients in the sixth to eighth decades of life and the overall 5-year survival rate is 60-70%. METHODS: After the establishment of the novel myxofibrosarcoma cell lines MUG-Myx1, cells were characterized using short tandem repeat (STR), copy number variation (CNV), and genotype/loss-of-heterozygosity (LOH) analyses. The growth behaviour of the cells was analyzed with the xCELLigence system and an MTS assay. The tumourigenicity of MUG-Myx1 was proved in NOD/SCID mice. Additionally, a stem-like cell population with high enzymatic activity of aldehyde dehydrogenase 1 (ALDH1(high)) was isolated for the first time from myxofibrosarcoma cells using the Aldefluor® assay followed by FACS analysis. RESULTS: The frozen primary parental tumour tissue and the MUG-Myx1 cell line showed the same STR profile at the markers D3S1358, TH01, D21S11, D18S51, Penta E, D5S818, D13S317, D7S820, D16S539, CSF1PO, Penta D, Amelogenin, D8S1179, TPOX, and FGY. Typically, myxofibrosarcoma gain and/or amplification was mapped to 7p21.3-q31.1, q31.1-q31.33, q33-q36.2, p21.3, p21.2, p14.1-q11.23, q31.33-q33, p21.2-p14.1, q11.23-q21.3, q36.2-q36.3, which, respectively are known to harbour tumour-associated genes, including TIF, BRAF, MLL3, SMO, and MET. Typically an LOH for myxofibrosarcoma on chr5 q21 was found. In addition, MUG-Myx1 ALDH1(high) cells showed an upregulation of the ABC transporter ABCB1 and ABCG2; higher c-Myc, E-cadherin and SOX-2 expression; and a higher potential for tumourigenicity and proliferation levels. CONCLUSION: The new myxofibrosarcoma cell line MUG-Myx1 was established to enrich the bank of publicly available cell lines, with respect to providing comprehensive genetic and epigenetic characterization. Furthermore, because of their tumourigenicity, the cell line is also suitable for in vivo experiments.
Ophthalmic Plastic and Reconstructive Surgery · 2018 · 9 citations
Orbital Myxofibrosarcoma: Case Report and Review of Literature
AbstractMyxofibrosarcoma is rarely found in the orbit, let alone as a primary orbital tumor. With this having only been previously reported 5 times in the literature, there is a very limited understanding of its presentation and course. Typical management involves surgical excision with or without postoperative radiotherapy. Low-grade malignancy, although rare to metastasize, still has a high rate of local recurrence and with each recurrence increases the risk of metastatic potential. With this in mind, analysis of each case is critical in better understanding the disease, and this case adds to the current literature.
Low‐grade myxofibrosarcoma invaded into the underlying skeletal muscle
AbstractMyxofibrosarcoma is a rare, soft-tissue sarcoma which is classified into three main subtypes according to cellularity and cell atypia: low, intermediate and high grade. A 44-year-old Japanese female presented with a low-grade myxofibrosarcoma on the left forearm. The lesion was completely resected. Histopathologically, the tumor was remarkably hypocellular and exhibited only mild atypia. However, it rapidly invaded into the underlying brachioradial muscle. The present case clearly indicated that a low-grade myxofibrosarcoma can invade into the deeper tissues including muscle even though its histological grade is very low.
Journal of Cancer and Tumor International · 2023 · 0 citations · open access
Anterior Thigh Myxofibrosarcoma with Management of Wide Excision and Modified Anterior Thigh Compartment Resection : A Case Report
AbstractIntroduction: Myxofibrosarcoma (MFS) is a type of malignancy from the group of malignant fibrous histiocytoma. Myfxofibrosarcoma is a type of soft tissue neoplasm that is aggressive. The clinical symptoms are not pathognomonic and the histological picture is very heterogeneous, often receiving delayed treatment and causing misdiagnosis. Complementary histochemical and immunohistochemical staining is mandatory to confirm the diagnosis of MFS. Extensive surgical treatment and followed by radiotherapy is the first choice of myxofibrosarcoma treatment.
 Case Presentation: A 54-years old woman complained of a lump on her left thigh that had been getting bigger for the past 2 years. The lump initially looked the size of a marble, then grew to the size of a tennis ball in the last 7 months. On physical examination, a mass was found in the left thigh area, a hard, fixed mass, the size of a tennis ball. Fine needle aspiration examination showed suspicious results for myxofibrosarcoma. The patient underwent a Magnetic Resonance Imaging examination in the left lower extremity area and underwent wide excision and anterior thigh compartment resection surgery.
 Discussion: Wide resection is the standard treatment for MFS [4]. The choice of procedure for each patient is different and should be based on tumor size, location, stage, surrounding neurovascular and bony elements, as well as functional and cosmetic considerations [4]. The minimum resection margin in MFS is at least 1 cm which aims to minimize the risk of local recurrence [4]. The recommended resection margin is at least 2 cm for MFS resection [4]. We had plan a 2 cm margin of the entire preoperative MRI enhancement area. It should be noted that the local recurrence rate for MFS in margin-negative resections is relatively high compared with other STS subtypes.
 Conclusion: We recommend Wide Excison and Modified Anterior Thigh compartment Resection is recommended procedure for anterior thigh myxofibrosarcoma. This procedure involves preserving uncontaminated thigh neurovascular, and only resecting one of the sarcoma-infiltrated muscle heads and preserving the other quadriceps muscle head of the thigh to maintain knee extension function. This paper is the first report on the successful treatment of anterior thigh myxofibrosarcoma without weakness of knee extension complication.
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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