DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for CIC-rearranged sarcoma — 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 moduleCIC-rearranged sarcoma 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 cic-rearranged 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
aldo-keto reductase family 1 member C2 (AKR1C2) — AKR1C2 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 ibpdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 4JTR · 1.3 Å · ligand IBUPROFEN (IBP). Experimental structure, not a prediction.
What the evidence adds up to
CIC-rearranged sarcoma is a very rare, highly aggressive soft tissue tumour of children and young adults, with no standard therapy established. A 2017 case report of a 14-year-old male with a colonic CIC-rearranged sarcoma describes death two months after diagnosis from peritoneal and pleural progression, despite wide excision and referral for chemotherapy. The authors state that resistance to chemotherapy is common. A 2023 case report of a 14-year-old girl describes successful application of the CWS-2009 treatment protocol, but provides no survival or response data for that patient.
A 2008 case report of follicular dendritic cell sarcoma of the neck — a different entity from CIC-rearranged sarcoma — describes a 49-year-old woman treated with surgical excision and five courses of COP plus PEG-liposomal doxorubicin. After five years of follow-up she was alive and in complete remission, with no haematological or cardiac toxicity reported. This regimen has not been tested in CIC-rearranged sarcoma.
A 2020 review of refractory paediatric sarcoma notes that almost one-third of patients present with metastasis at baseline and another one-third recur after initial treatment. It states that for treatment-refractory cases, options are limited to novel therapeutics, immunotherapy, targeted therapies, and metronomic therapies, but provides no specific outcome data for CIC-rearranged sarcoma. A 2024 epidemiological study of translocation-related sarcomas in Japan found that patients with translocation-related sarcomas had better overall survival (HR 0.71, 95% CI 0.63–0.81), metastasis-free survival (HR 0.75, 95% CI 0.67–0.84), and recurrence-free survival (HR 0.47, 95% CI 0.39–0.57) than patients without translocations, but this analysis did not isolate CIC-rearranged sarcoma from other translocation subtypes. A 2023 review of local therapies for metastatic sarcoma discusses multidisciplinary management but provides no data specific to CIC-rearranged sarcoma.
What is still missing: prospective trials or even adequately sized retrospective series focused specifically on CIC-rearranged sarcoma; any validated systemic therapy regimen; any biomarker for response; and funding for the international collaboration needed to study this ultra-rare tumour.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Journal of Experimental & Clinical Cancer Research · 2008 · 17 citations · open access
Follicular dendritic cell sarcoma of the neck: Report of a case treated by surgical excision and COP plus (PEG)-liposomal doxorubicin
AbstractBACKGROUND: Follicular dendritic cell (FDC) sarcoma is a rare neoplasm arising in lymph nodes but also in extranodal sites from accessory cells of the immune system that are essential for the function of antigen presentation and germinal center reaction regulation. FDC sarcoma has a significant recurrent and metastatic potential and for these reason it should be viewed as an intermediate grade malignancy. METHODS: We report the case of a 49-year old woman patient who showed persistent, enlarged, hard, cervical lymph node. The most common histologic feature was the presence of oval to spindle cells with elongated nuclei, vesicular or stippled chromatin and scant eosinophilic cytoplasm. Immunohistochemically, tumor cells were diffusely positive for follicular dendritic cell markers CD21, CD23 and negative for cytokeratin.The patient after complete excision of the lymph node underwent five courses of adjuvant chemotherapy with COP plus PEG-liposomal doxorubicin, considering the propensity of the tumor to metastasize. RESULTS: No hematological or cardiac toxicity were registered and among the other extra hematological effects only transitory palmar erythrodysesthesia is worthy of mention. After a follow up of 5 years the patient is alive and in CR. CONCLUSION: These results suggest that this therapeutic modality may be useful in the management of FDC sarcoma.
OncoTargets and Therapy · 2020 · 14 citations · open access
<p>Management of Refractory Pediatric Sarcoma: Current Challenges and Future Prospects</p>
AbstractPaediatric sarcomas are a heterogeneous group of disorders constituting bone sarcoma and various soft tissue sarcomas. Almost one-third of these presents with metastasis at baseline and another one-third recur after initial curative treatment. There is a huge unmet need in this cohort in terms of curative options and/or prolongation of survival. In this review, we have discussed the current treatment options, challenges and future strategies of managing relapsed/refractory paediatric sarcomas. Upfront risk-adapted treatment with multidisciplinary management remains the main strategy to prevent future recurrence or relapse of the disease. In the case of limited local and/or systemic relapse or late relapse, initial multimodality management can be administered. In treatment-refractory cases or where cure is not feasible, the treatment options are limited to novel therapeutics, immunotherapeutic approach, targeted therapies, and metronomic therapies. A better understanding of disease biology, mechanism of treatment refractoriness, identifications of driver mutation, the discovery of novel targeted therapies, cellular vaccine and adapted therapies should be explored in relapsed/refractory cases. Close national and international collaboration for translation research is needed to fulfil the unmet need.
BMC Research Notes · 2017 · 7 citations · open access
Round cell sarcoma of the colon with CIC rearrangement
AbstractBACKGROUND: The CIC-rearranged sarcoma is a very rare highly aggressive malignant soft tissue group of tumors. It has recently been described as highly aggressive soft tissue tumors of children and young adults sharing similar morphological features with the Ewing sarcoma. The digestive localization is exceptional. CASE PRESENTATION: A 14-year-old male presented with a history of abdominal pain for 1 year, which increased in intensity over the last 2 months. Imaging findings showed a large heterogeneous mesenteric mass on the left flank of the abdomen. Exploratory laparotomy was performed and revealed a large cystic hypervascularized mass depending on the transverse colon and mesocolon. A wide excision of the lesion was performed with segmental colectomy. No postoperative complications were noted. The microscopic examination revealed a vaguely nodular growth of undifferentiated small round cells, arranged in solid sheets separated by thin fibrous septa with a scarce stroma. After an uncomplicated post-operative course, the patient was referred for chemotherapy. The patient died 2 months later with a peritoneal and pleural progression. CONCLUSIONS: The CIC-rearranged sarcoma is an aggressive tumor. There is no standard therapy for this rare disease. Their treatment includes surgery and chemotherapy. Resistance to chemotherapy is common. Further publications and studies will help to determine a standard therapy for this rare disease.
American Society of Clinical Oncology Educational Book · 2023 · 6 citations · open access
Local Therapies for Metastatic Sarcoma: Why, When, and How?
AbstractManagement of patients with advanced sarcoma has been evolving in recent decades, from a one-fit-all perspective to a more refined, personalized, and multidisciplinary approach. In parallel, the evolution of local therapies (radiotherapy, surgical and interventional radiology techniques) has contributed to the improvement of survival of patients with advanced sarcoma. In this article, we review the evidence regarding local treatments in advanced sarcoma, as well as its integration with systemic therapies, to provide the reader a wider and deeper perspective on the management of patients with metastatic sarcoma.
Translocation in bone and soft tissue sarcomas: a comprehensive epidemiological investigation
AbstractBACKGROUND: Limited epidemiological research has focused on translocations in soft tissue sarcomas, with no studies on bone sarcomas. This study aimed to clarify the epidemiology, prognosis, and genetic information of translocation-related sarcoma (TRS) and non-TRS patients. MATERIALS AND METHODS: This retrospective cohort study used data from the Bone and Soft Tissue Tumor Registry in Japan (BSTTRJ) (2001-2019), the Kyushu University Hospital (KUH) repository (2001-2021), and a publicly available online dataset (MSK). The patients were categorized into TRS and non-TRS groups, and epidemiological, prognostic, and mutational diversity were compared. RESULTS: This study included 25 383 participants, of whom 4864 (19.2%) were TRS and 20 519 (80.8%) were non-TRS patients. TRS patients had significantly younger onset ages (median: 43 years, interquartile range: 29-59 years) than non-TRS patients (median: 63 years, interquartile range: 46-73 years). In the MSK cohort, microsatellite instability and tumor mutation burden scores in non-TRS were higher than in TRS, although they were rather low compared with the pan-cancer analysis. In the BSTTRJ cohort, survival analyses with the propensity score matching revealed that patients with TRS had better overall [hazard ratio (HR): 0.71, 95% confidence interval (CI) 0.63-0.81], metastasis-free (HR: 0.75, 95% CI 0.67-0.84), and recurrence-free (HR: 0.47, 95% CI 0.39-0.57) survival. CONCLUSIONS: This study highlights differences in the epidemiology and genetic rearrangements of sarcoma.
Russian Journal of Archive of Pathology · 2023 · 0 citations
CIC-rearranged sarcoma: a case report and literature review
AbstractCIC-rearranged sarcoma is a rare and extremely aggressive tumor that occurs mainly in soft tissues. Despite the fact that identification of a characteristic genetic rearrangement is necessary to verify the diagnosis, in most cases, the correct diagnosis can be made by comparing histological signs and a characteristic immunophenotype, which greatly speeds up the diagnosis. The article describes a case of CIC-rearranged sarcoma in a 14-year girl with the successful application of the CWS-2009 treatment protocol.
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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