DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for Paraganglioma — screening already-approved drugs against its 46-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleParaganglioma maps to a 46-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 paraganglioma 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
endothelial PAS domain protein 1 (EPAS1) — EPAS1 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 furan-2-ylmethyldrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 3H82 · 1.5 Å · ligand N-(furan-2-ylmethyl)-2-nitro-4-(trifluoromethyl)aniline (020). Experimental structure, not a prediction.
What the evidence adds up to
A review of 14 patients treated between 1986 and 1996 found 20 tumours, with 70% in the head and neck and 25% in the retroperitoneum. Three patients (21%) had a familial history. Clinically functioning tumours occurred in 3 patients (17%), presenting with uncontrolled hypertension. Malignancy, defined by metastasis rather than histology, occurred in 2 patients (10%) with spread to lymph nodes and vertebrae. All patients underwent surgical resection; late mortality occurred in 2 patients (12.5%) at 3 and 5 years from unrelated causes, and 4 patients (25%) were lost to follow-up. Three patients (18.7%) developed new primaries, and one patient (6%) had a recurrence after 20 disease-free years. A separate series of 26 patients treated between 2000 and 2007 reported 27 paragangliomas, with 51.8% at the carotid bifurcation. No functional tumours were found. Malignancy was documented in one case (3.8%). Preoperative embolisation was performed in 88% of operated tumours. Vascular injury occurred in 6 patients (23%), transient cranial nerve deficit in 4 (15.3%), permanent Horner syndrome in 2 (7.6%), cerebrospinal fluid leak in 1 (3.7%), and postoperative stroke in 1 (3.7%). Two patients with skull base extension received radiotherapy and had significant symptomatic relief.
A 2024 discussion describes systemic targeted radiotherapies, 131I-MIBG and 177Lu-DOTATATE, as a mainstay for metastatic paraganglioma, but provides no new efficacy data from a controlled trial. A 2013 case report describes a 69-year-old man with mediastinal paraganglioma metastatic to bone who received sorafenib 400 mg twice daily for six months after radiotherapy and etoposide-cisplatin chemotherapy. A dramatic reduction in tumour volume was observed, and the patient achieved a partial response. The authors note that no effective systemic therapies were available at the time and suggest further investigation of sorafenib. A 2022 case report describes a 45-year-old woman with malignant paraganglioma who received intravenous and peritoneal perfusion chemotherapy, then radiotherapy and molecular targeted therapy with apatinib after developing liver and bone metastases. Disease control was poor.
The evidence for drug treatment of paraganglioma remains limited to single case reports and expert discussion. No randomised trial has tested sorafenib, apatinib, 131I-MIBG, or 177Lu-DOTATATE in this disease. The natural history is highly variable, with some patients remaining disease-free for decades after surgery and others developing late recurrences or metastases. What is missing is any prospective trial with sufficient sample size to establish whether any systemic agent improves progression-free or overall survival, and a reliable method to stratify patients by risk of metastasis or progression.
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 Surgical Oncology · 2000 · 90 citations
Paragangliomas?A decade of clinical experience
AbstractBACKGROUND AND OBJECTIVES: This study is a review of 14 patients with paragangliomas between 1986 and 1996. The purpose was to determine the sites of origin, clinical manifestations and analyze the benefits of different treatment modalities. METHODS: There were 20 tumors in 14 patients. Three (21.0%) of the patients had familial history. There were 7 (50%) females and 7 (50%) males. Anatomically 14 (70%) tumors were in head and neck, 5 (25%) were in the retroperitoneum, one (5%) was in the heart. Of the head and neck tumors 9 (64.25%) were in the carotid body, 3 (21.42%) were found in the vagus, and 2(14.33%) were found in the middle ear. The tumor found in the heart was in the atrial septum. The clinical behavior of paragangliomas is determined by cellular characteristics, secreting capabilities and tumor location. The symptoms and signs depend on the site of origin and the stage at which it presents. The clinically functioning tumors were 3 (17%) in our experience and they typically present with uncontrolled hypertension. The carotid body and mediastinal tumors usually manifested as asymptomatic masses. The intravagal tumors presented with paresis of the nerve. Malignancy rarely occurs and is defined by the existence of metastasis rather than by histology. In our series 2 (10%) of the patients presented with metastasis to lymph nodes, and the vertebrae. The diagnoses in our patients were established by CT and MRI scanning. Angiography was performed in 5 patients with carotid body tumor, two of whom underwent therapeutic embolization to reduce the tumor size. The mainstay of treatment was surgical removal, though radiation has been advocated for patients who cannot undergo surgery. RESULTS: All patients underwent successful surgical resection of the tumor after appropriate preoperative preparation. Late mortality occurred in two (12.5%) patients at 3 and 5 years from unrelated etiology. Four (25%) patients were lost to follow-up. Three (18.7%) patients developed new primaries, two of them at two years and one after 8 years. One (6%) patient developed recurrent paraganglioma after remaining disease free for 20 years. CONCLUSION: In conclusion, paragangliomas are rare with multicentricity being more common in patients with familial history. The malignant potential of the tumor is determined by metastasis as there are no characteristic cellular change. Aggressive surgery is mandatory to obtain disease free survival with low morbidity and mortality. Recurrences can also be successfully operated with low morbidity.
Journal of Craniofacial Surgery · 2009 · 28 citations
Management of Paragangliomas in Otolaryngology Practice
AbstractBACKGROUND AND AIMS: Paragangliomas of the head and neck are highly vascular lesions originating from paraganglionic tissue located at the carotid bifurcation (carotid body tumors), along the vagus nerve (vagal paragangliomas), and in the jugular fossa and tympanic cavity (jugulotympanic paragangliomas) and should be considered in the evaluation of all lateral neck masses. The aim of this study is to review an institutional experience in the management of these tumors. MATERIALS AND METHODS: Twenty-six patients with 27 paragangliomas were treated in our institution during a period of 7 years (2000-2007). There were 15 women (57.6%) and 11 men (42.4%) with a mean age of 33.5 years. A painless lateral neck mass was the main finding in 16 patients (61.5%). There was no evidence of a functional tumor. Carotid angiography was performed on all of our patients (100%) to define the vascular anatomy of the lesion. Twenty-two paragangliomas (of the 25 operated paragangliomas; 88%) underwent selective embolization of the major feeding arteries. We performed surgery on 24 (92.3%) patients. Two patients were treated with radiotherapy. RESULTS: Most lesions were paragangliomas of the carotid bifurcation (n = 14 [51.8%]), whereas 6 patients were diagnosed with jugular (22.2%), 1 with a vagal (3.7%), 1 with a tympanic paraganglioma (3.7%), 2 with jugulotympanic paraganglioma (7.4%), and 1 with laryngeal paraganglioma (3.7%). In 1 patient (3.8%), bilateral paragangliomas in the carotid bifurcation were detected. There was an evidence of malignancy in all cases (3.8%). Preoperative embolization has proven successful in reducing tumor vascularity in approximately 22 (of 25 who accepted surgery; 88%) paraganglioma patients. The common preoperative complication was vascular injury, which occurred in 6 (23%) of 26 patients; the main postoperative complication was transient cranial nerve deficit in 4 (15.3%) of 26 patients; and a permanent Horner syndrome was documented in 2 patients (7.6%). Cerebrospinal fluid leak occurred in 1 patient (3.7%). Postoperatively, stroke was occurred in 1 patient (3.7%). Two patients with jugular paraganglioma were treated with irradiation because of skull base extension with significant symptomatic relief. CONCLUSIONS: The primary therapeutic option for paragangliomas is complete excision of tumor with preservation of vital neurovascular structures. Combined therapeutic approach with preoperative selective embolization followed by surgical resection is the safe and the effective method for complete excision of the tumors with a reduced morbidity rate.
The Journal of Clinical Endocrinology & Metabolism · 2024 · 14 citations · open access
Approach to the Patient: Concept and Application of Targeted Radiotherapy in the Paraganglioma Patient
AbstractParagangliomas can metastasize, posing potential challenges both in symptomatic management and disease control. Systemic targeted radiotherapies using 131I-MIBG and 177Lu-DOTATATE are a mainstay in the treatment of metastatic paragangliomas. This clinical scenario and discussion aim to enhance physicians' knowledge of the stepwise approach to treat these patients with paraganglioma-targeted radiotherapies. It comprehensively discusses current approaches to selecting paraganglioma patients for targeted radiotherapies and how to choose between the two radiotherapies based on specific patient and tumor characteristics, when either therapy is feasible, or one is superior to another. The safety, efficacy, toxicity profiles, and optimization of these radiotherapies are also discussed, along with other therapeutic options including radiotherapies, available for patients besides these two therapies. Perspectives in radiotherapies of paraganglioma patients are outlined since they hold promising approaches in the near future that can improve patient outcomes.
OncoTargets and Therapy · 2013 · 8 citations · open access
Successful treatment of paraganglioma with sorafenib: a case report and brief review of the literature
AbstractINTRODUCTION: To date, no effective systemic therapies have been made available for paraganglioma. However, multiple mutations in susceptibility genes have been identified that are potential targets for sorafenib, an oral multitargeted tyrosine-kinase inhibitor. CASE PRESENTATION: We report the case of a 69-year-old Chinese man with mediastinal paraganglioma that had metastasized to the bone. The paraganglioma responded to sorafenib, a novel multi-tyrosine kinase inhibitor that targets angiogenesis, the Raf-kinase pathway, the platelet-derived growth factor Ret, and c-Kit. The patient was diagnosed as having paraganglioma after biopsy of the mediastinal mass. We first treated the patient with radiotherapy. Then he tolerated an etoposide-and-cisplatin chemotherapy regimen. Subsequently, he received 6 months of maintenance treatment with sorafenib (400 mg twice daily). A dramatic reduction in tumor volume was observed. At present, the patient has achieved a partial response, and his clinical status remains unchanged. CONCLUSION: We suggest that sorafenib should be further investigated in the management of patients with paraganglioma.
World Journal of Clinical Cases · 2022 · 2 citations · open access
Diagnostic features and therapeutic strategies for malignant paraganglioma in a patient: A case report
AbstractBACKGROUND: Paragangliomas and extra-adrenal pheochromocytomas are uncommon neuroendocrine tumors with ubiquitous distribution. Malignant paraganglioma is a relatively rare entity. We report the treatment and pathological characteristics of a patient with malignant paraganglioma, and summarize the latest advances in the treatment of malignant paraganglioma based on a literature review. CASE SUMMARY: A 45-year-old Chinese woman presented to the hospital due to pain in the waist (right side) and right buttock, and was diagnosed as malignant paraganglioma after the placement of ureteral stent, implantation of ileus catheter, and transvaginal removal of the vaginal mass. After relief of intestinal obstruction, the patient received intravenous chemotherapy and peritoneal perfusion chemotherapy. Although her pelvic mass disease was stable, she developed multiple liver metastases and bone metastases. Due to the development of spinal cord compression, she underwent orthopedic surgery, followed by radiotherapy, and molecular targeted therapy with apatinib, but with poor disease control. CONCLUSION: Clinical management of paraganglioma is challenging for endocrinologists and oncologists. Prospective studies are required to develop standardized therapeutic strategies for malignant paragangliomas.
Scholars Journal of Medical Case Reports · 2025 · 0 citations · open access
Efficience of Radiotherapy in Unresectable Carotid Paraganglioma
AbstractParagangliomas are benign tumor. The first line treatment is surgery. However when this treatment is not feasible, radiation therapy remains an effective therapeutic alternative, that allows local control with acceptable morbidity, demonstrated by the clinical case presented in this publication. The follow up characterised by regression or stability of the lesion and improvment of neurological symptoms.
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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