DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for angiosarcoma — screening already-approved drugs against its 48-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleAngiosarcoma maps to a 48-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
Angiosarcoma is a malignancy of the vascular endothelium. Its oncogenesis is frequently driven by inappropriate activation of the VEGFR family (VEGFR-1/2/3) and related receptor tyrosine kinases, and a subset carries high-level MYC amplification. That biology makes the already-approved anti-angiogenic drug class a rational, safety-characterised starting point for repurposing research.
approvedPazopanibApproved drugapprovedSorafenibApproved drugapprovedSunitinibApproved drug
Structures already discussed alongside angiosarcoma in the retrieved literature, rendered from public PubChem SMILES. Which drugs appear here reflects the evidence found, not a ranked prediction.
Molecular view
VEGFR2 (KDR) — juxtamembrane and kinase domains — Crystal structure of VEGFR2 — the receptor tyrosine kinase whose inappropriate activation drives much of angiosarcoma biology — in complex with sorafenib, an already-approved multikinase inhibitor. The protein backbone is drawn as a cartoon; the drug sits in the ATP-binding cleft as sticks. This is an experimentally determined structure from the Protein Data Bank, not a prediction.
Loading structure…
helix sheet baxdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 4ASD · ligand Sorafenib (BAX). Experimental structure, not a prediction.
What the evidence adds up to
Angiosarcoma is rare and unforgiving. In the largest single-institution series (125 patients over 14 years) overall five-year survival was 31%, and for unresectable disease doxorubicin-based regimens bought 3.7 to 5.4 months of progression-free survival. Paclitaxel did better, but only in one place: 6.8 months for scalp disease against 2.8 months below the clavicle. A real-world Korean cohort put first-line weekly paclitaxel at a 52% objective response rate, 5.7 months median progression-free survival and 18.6 months overall survival. These are the numbers a new therapy has to beat.
The biological rationale for hitting VEGFR is strong: angiosarcoma arises from vascular endothelium and a subset carries activating VEGFR2 mutations or high-level MYC amplification. Yet the phase II record for anti-angiogenic tyrosine kinase inhibitors — bevacizumab, sunitinib, sorafenib, pazopanib — is sobering: response rates and progression-free survival were generally low, even though individual patients achieved durable disease stabilization. One review of eight pazopanib-treated cases concluded plainly that it brought no remarkable improvement. The signal is real but unselected patients dilute it.
Two findings point at where the opportunity actually sits. First, molecular selection: VEGFR2- and VEGFR3-amplified tumours have responded to pazopanib, which suggests the drug class works when the target is genuinely there. Second, repurposing: propranolol — an off-patent generic beta-blocker costing almost nothing — cut the proliferative index of a stage T2 cutaneous angiosarcoma by roughly 34% after a single week of monotherapy, and in combination with standard therapy produced extensive regression in a tumour type whose two-year survival at that stage is otherwise 0%. Checkpoint inhibitors add a third axis, with five of seven patients showing partial response at twelve weeks in a small series.
Read together, the literature does not say that angiosarcoma lacks candidate drugs. It says the candidates exist, several are already approved and cheap, and what is missing is the money and the trial design to test them in the right patients. That gap is economic, not scientific — which is precisely the gap DeCure exists to close.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
The Cancer Journal · 2005 · 419 citations
A 14-Year Retrospective Review of Angiosarcoma
AbstractPURPOSE: Angiosarcoma is a rare vascular malignancy, and there are few published data to guide chemotherapy treatment decisions. We present a retrospective analysis of angiosarcoma encompassing all anatomic sites of disease presenting to a single institution over a 14-year period. Characteristics at presentation and prognostic factors are reviewed. For patients with unresectable disease, progression-free survival with various chemotherapy regimens is described. PATIENTS AND METHODS: Pathological confirmation of all cases was performed before they were included in this analysis. One hundred twenty-five patients with angiosarcoma were seen and treated between January 1, 1990 and December 31, 2003. RESULTS: Angiosarcoma showed marked variation by anatomic site regarding gender ratio, median age at diagnosis, overall survival, and response to chemotherapy. Overall 5-year survival was 31% for angiosarcoma. Superficial depth and negative microscopic surgical margins correlated with longer overall survival, but tumor size did not reach significance as a prognostic factor. For unresectable angiosarcoma, doxorubicin based regimens yielded progression-free survival of 3.7-5.4 months. Paclitaxel achieved a progression-free survival of 6.8 months for scalp angiosarcoma and 2.8 months for sites below the clavicle. DISCUSSION: Angiosarcoma is an aggressive malignancy characterized by biologic heterogeneity at different anatomic sites and relative sensitivity to paclitaxel and doxorubicin.
Journal for ImmunoTherapy of Cancer · 2019 · 184 citations · open access
Angiosarcoma patients treated with immune checkpoint inhibitors: a case series of seven patients from a single institution
AbstractBACKGROUND: Angiosarcoma is an uncommon endothelial malignancy and a highly aggressive soft tissue sarcoma. Due to its infiltrative nature, successful management of localized angiosarcoma is often challenging. Systemic chemotherapy is used in the metastatic setting and occasionally in patients with high-risk localized disease in neoadjuvant or adjuvant settings. However, responses tend to be short-lived and most patients succumb to metastatic disease. Novel therapies are needed for patients with angiosarcomas. METHODS: We performed a retrospective analysis of patients with locally advanced or metastatic angiosarcoma, who were treated with checkpoint inhibitors at our institution. We collected their clinical information and outcome measurements. In one patient with achieved complete response, we analyzed circulating and infiltrating T cells within peripheral blood and tumor tissue. RESULTS: We have treated seven angiosarcoma (AS) patients with checkpoint inhibitors either in the context of clinical trials or off label [Pembrolizumab + Axitinib (NCT02636725; n = 1), AGEN1884, a CTLA-4 inhibitor (NCT02694822; n = 2), Pembrolizumab (n = 4)]. Five patients had cutaneous angiosarcoma, one primary breast angiosarcoma and one radiation-associated breast angiosarcoma. At 12 weeks, 5/7 patients (71%) had partial response of their lesions either on imaging and/or clinical exam and two (29%) had progressive disease. 6/7 patients are alive to date and, thus far, 3/7 patients (43%) have progressed (median 3.4 months)- one achieved partial response after pembrolizumab was switched to ongoing Nivolumab/Ipilimumab, one died of progressive disease at 31 weeks (primary breast angiosarcoma) and one was placed on pazopanib. One patient had a complete response (CR) following extended treatment with monotherapy AGEN1884. No patient experienced any ≥ grade 2 toxicities. CONCLUSIONS: This case series underscores the value of targeted immunotherapy in treating angiosarcoma. It also identifies genetic heterogeneity of cutaneous angiosarcomas and discusses specific genetic findings that may explain reported benefits from immunotherapy.
Current Opinion in Oncology · 2010 · 169 citations
Inhibiting the VEGF–VEGFR pathway in angiosarcoma, epithelioid hemangioendothelioma, and hemangiopericytoma/solitary fibrous tumor
AbstractPURPOSE OF REVIEW: This review highlights the current body of knowledge regarding the role of the vascular endothelial growth factor (VEGF) and its receptor (VEGFR) in angiosarcoma, epithelioid hemangioendothelioma (EHE), and hemangiopericytoma/solitary fibrous tumor (HPC/SFT). Therapeutic agents that target this pathway are reviewed. RECENT FINDINGS: Several phase II trials in advanced soft tissue sarcoma patients have investigated the efficacy of bevacizumab, an anti-VEGF antibody, as well as sunitinib, sorafenib, and pazopanib, VEGFR tyrosine kinase inhibitors (TKIs). Although response rates and progression-free survival periods were generally low, several angiosarcoma, EHE, and HPC/SFT patients demonstrated response or durable disease stabilization on these therapies. Biological mechanisms underlying the activity of these agents in angiosarcoma, EHE, and HPC/SFT are poorly understood. Some angiosarcoma tumors, however, harbor specific activating mutations in VEGFR2, which may be effectively targeted by VEGFR TKIs. SUMMARY: Inhibition of the VEGF/VEGFR pathway may be a rational and effective therapy for certain patients with angiosarcoma, EHE, and HPC/SFT, but more studies are needed to confirm these findings and to identify which patients will benefit from these agents.
Growth Attenuation of Cutaneous Angiosarcoma With Propranolol-Mediated β-Blockade
AbstractIMPORTANCE: Patients with stage T2 multilesion angiosarcomas of the scalp and face that are larger than 10 cm demonstrate a 2-year survival rate of 0%. To our knowledge, major therapeutic advances against this disease have not been reported for decades. Preclinical data indicate that blocking β-adrenergic signaling with propranolol hydrochloride disrupts angiosarcoma cell survival and xenograft angiosarcoma progression. OBSERVATIONS: A patient presented with a β-adrenergic-positive multifocal stage T2 cutaneous angiosarcoma (≥20 cm) involving 80% of the scalp, left forehead, and left cheek, with no evidence of metastasis. The patient was immediately administered propranolol hydrochloride, 40 mg twice a day, as his workup progressed and treatment options were elucidated. Evaluation of the proliferative index of the tumor before and after only 1 week of propranolol monotherapy revealed a reduction in the proliferative index of the tumor by approximately 34%. A combination of propranolol hydrochloride, 40 mg 3 times a day, paclitaxel poliglumex, 2 mg/m2 infused weekly, and radiotherapy during the subsequent 8 months resulted in extensive tumor regression with no detectable metastases. CONCLUSIONS AND RELEVANCE: Our data suggest that β-blockade alone substantially reduced angiosarcoma proliferation and, in combination with standard therapy, is effective for reducing the size of the tumor and preventing metastases. If successful, β-blockade could be the first major advancement in the treatment of angiosarcoma in decades.
Clinical Sarcoma Research · 2016 · 13 citations · open access
A Korean single-center, real-world, retrospective study of first-line weekly paclitaxel in patients with metastatic angiosarcoma
AbstractBACKGROUND: Angiosarcoma is a rare subgroup of soft tissue sarcomas associated with poor prognosis, but paclitaxel has been shown to be active in pretreated metastatic disease. We investigated the efficacy and safety of weekly paclitaxel as first-line chemotherapy in adult patients with metastatic angiosarcoma. METHODS: A retrospective study using the Samsung Medical Center (Seoul, Korea) cancer chemotherapy registry was performed on 21 consecutive patients with angiosarcoma who were treated with weekly paclitaxel as first-line therapy for metastatic disease between Oct. 2008 and Dec. 2014. We excluded patients who were enrolled in clinical trials to ensure the results would reflect the real-world outcomes obtained in a daily clinical setting. Endpoints included efficacy in terms of response rate, progression-free survival (PFS), overall survival (OS) and safety. RESULTS: Among 21 patients, 15 (71 %) were male and the median age was 53 years (range, 24-76). Primary sites of angiosarcoma were the visceral organs (33 %), scalp (29 %) and heart (23 %). The median number of metastatic sites was two (range, 1-5) with the lungs being the most frequently involved site. Weekly paclitaxel was generally well tolerated: the major hematologic toxicity was grade 1/2 anemia (24 %). Among non-hematologic toxicities, grade 1/2 peripheral neuropathy was most commonly observed (67 %). Objective response was observed in 11 (52 %) patients (4 complete and 7 partial responses). With a median follow-up of 21 months, the estimated median PFS and OS were 5.7 months (95 % CI 5.1-6.3) and 18.6 months (95 % CI 9.9-27.3), respectively. CONCLUSIONS: In this retrospective study, first-line chemotherapy with weekly paclitaxel demonstrated clinically relevant efficacy and tolerability in unselected Korean patients with metastatic angiosarcoma. It is encouraging that response rate and PFS for Korean patients were similar to those reported in Western reports.
Angiology Open Access · 2013 · 9 citations · open access
Aberrations in Angiogenic Signaling and MYC Amplifications are Distinguishing Features of Angiosarcoma
AbstractAngiosarcomas are very aggressive, rare malignant tumors that originate from vascular or lymphatic vessels and primarily occur following chemical exposure or radiation therapy. Tumor response to either chemotherapy, radiation, or novel anti-angiogenic therapeutics is very low, and because little is known regarding the aberrant signaling that controls these tumors, personalized treatment options for many of these patients are lacking. In this review, we summarize several recent findings regarding the genomics of angiosarcomas, including new discoveries regarding aberrant angiogenic signaling and Myc amplification as key features of this tumor type.
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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