DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for giant cell tumor — screening already-approved drugs against its 2-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleGiant cell tumor maps to a 2-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
Structures already discussed alongside giant cell tumor in the retrieved literature, rendered from public PubChem SMILES. Which drugs appear here reflects the evidence found, not a ranked prediction.
Molecular view
Native structure of Farnesyl Pyrophosphate Synthase from Pseudomonas aeruginosa PA01, — Ibandronate has a real, experimentally solved structure in complex with this target (PDB 4UMJ, 1.85 Å). This is the drug's own deposited structure, not a prediction, and confirms it is a structurally characterised molecule rather than an untested guess.
Loading structure…
helix sheet bfqdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 4UMJ · 1.85 Å · ligand Ibandronate (BFQ). Experimental structure, not a prediction.
What the evidence adds up to
Giant cell tumour of bone is a rare primary bone tumour, typically an expanding osteolytic lesion. A 1998 case report describes a 24-year-old woman with a giant cell tumour located entirely within the sacral spinal canal, with no bone involvement, presenting with radicular pain. Complete surgical resection led to full recovery with no local regrowth or metastasis during 20 months of follow-up. The report states that the treatment of choice is complete surgical resection, that radiotherapy is recommended for subtotal resection, and that recurrence and metastasis are not uncommon.
A 1997 veterinary study on canine and feline neoplasias distinguishes neoplastic giant cells from reactive (non-neoplastic) giant cells in paraffin sections. Neoplastic giant cells have polymorphic nuclei, can show atypical mitosis, and are MIB 1 positive and tartrate resistant acid phosphatase (TRAP) negative. Osteoclast-like giant cells are MIB 1 negative and TRAP positive. The study notes that in human medicine the presence of neoplastic giant tumour cells is an index for poor prognosis, and recommends that diagnoses specify both the tumour entity and the giant cell type.
Several reviews from 2018, 2020, and 1997 (the last being a Buddhist Chinese-Sanskrit dictionary entry that also discusses polyploidy) describe polyploid giant cancer cells (PGCCs) in human solid tumours. Their frequency increases after hypoxia, radiation, and chemotherapy. Although these cells were previously thought to be senescent and non-proliferative, recent evidence indicates they can remain viable and metabolically active, and can produce daughter cells with tumourigenic and stem-like properties through asymmetric cell division (neosis). The reviews link PGCCs to metastasis, recurrence, drug resistance, and radio-resistance. The 2018 commentary notes that most preclinical drug discovery approaches may not account for delayed responses associated with dormant giant cells.
What is still missing are validated molecular targets to prevent PGCC formation or eliminate existing PGCCs, and clinical trial designs that account for the dormant, non-proliferative phase of these cells. No drug is mentioned in any of these abstracts.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Cancers · 2018 · 188 citations · open access
Roles of Polyploid/Multinucleated Giant Cancer Cells in Metastasis and Disease Relapse Following Anticancer Treatment
AbstractTumors and tumor-derived cell lines contain polyploid giant cells with significantly elevated genomic content, often with multiple nuclei. The frequency of giant cells can increase markedly following anticancer treatment. Although giant cells enter a dormant phase and therefore do not form macroscopic colonies (aggregates of ≥50 cells) in the conventional in vitro colony formation assay, they remain viable and metabolically active. The purpose of this commentary is to underscore the potential importance of polyploid/multinucleated giant cells in metastasis and cancer recurrence following exposure to anticancer agents. We also discuss the possibility that most preclinical (cell-based and animal model) drug discovery approaches might not account for delayed responses that are associated with dormant giant cells.
A new bisphosphonate treatment option for giant cell tumors
AbstractTreatment of giant cell tumors (GCT) especially in the vertebrae remains controversial. With multidisciplinary treatments, their results are still insufficient. Moreover, GCT shows the potential for malignant transformation and metastasis, additional options such as adjuvant medication must be considered. We report favorable results in three consecutive cases diagnosed with GCT of the spine which were treated with radiotherapy and bisphosphonate (BP) as a new treatment option, and present a review of the literature and a comparison with these case reports.
Administration of Sodium Ibandronate in the Treatment of Complicated Giant Cell Tumor of the Spine
AbstractSTUDY DESIGN: Case study. OBJECTIVE: To present three complicated cases of giant cell tumor of the spine treated with sodium ibandronate. SUMMARY OF BACKGROUND DATA: Spinal giant cell tumors are a rare clinical entity with a high recurrence rate after operation. Furthermore, complete resection of such lesions remains a challenging surgical problem. Up to this point, no effective adjuvant therapy has been reported for primary or recurrent spinal giant cell tumors. METHODS: One patient with a recurrent giant cell tumor of the seventh thoracic vertebra, one patient with a fifth lumbar vertebral giant cell tumor, and one patient with recurrent giant cell tumor of the sacrum were treated with sodium ibandronate either postoperatively or upon recurrence of the tumor. RESULTS: The first patient with recurrent thoracic giant cell tumor recovered both clinically and radiologically after treatment with sodium ibandronate without reoperation at 6-years follow-up. The second patient also recovered with no recurrence of the tumor at 4-years follow-up. In the third case, although not fully recovered, the recurrent sacral tumor was under control after treatment with sodium ibandronate at 2-years follow-up. CONCLUSION: These case studies demonstrate the potential promise of using sodium ibandronate in the treatment of primary and recurrent giant cell tumors of the spine. Furthermore, clinical evaluation should be performed in future studies.
Zentralblatt für Veterinärmedizin Reihe A · 1997 · 15 citations
Methods for the Differentiation of Giant Cells in Canine and Feline Neoplasias in Paraffin Sections
AbstractIn the following study cells with at least two cell nuclei are addressed as giant cells. In 47 biopsies of feline neoplasias (fibrosarcoma, haemangioendothelsarcoma, mammary adenocarcinoma, osteoidsarcoma, complex sarcoma), and 25 biopsies of canine neoplasias (malignant seminoma, mammary adenocarcinoma, haemangioendothelsarcoma, fibrosarcoma, osteoblastic sarcoma, complex sarcoma) giant cells are distinguished either as neoplastic giant cells or as reactive (non-neoplastic) giant cells. Cell nuclei of neoplastic giant cells which are labelled with the monoclonal antibody MIB 1 are mitotic active; cell nuclei are polymorph and can show atypical mitosis; the cytoplasmic reaction with tartrate resistant acid phosphatase (TRAP) is negative. Negative reactions with MIB 1, positive TRAP staining and homogeneous cell nuclei are distinctive for osteoclast-like glant cells. Other non-neoplastic giant cells (e.g. foreign body cells, Langhans-giant cells) are negative with both MIB 1 and TRAP. Double staining of paraffin sections is possible. Routine formalin-fixation, embedding in paraffin and decalcifying tissue samples do not interfere with MIB 1 immunoreactions or TRAP reactions. Methodological modifications that were necessary for the preparation of paraffin sections from canine and feline tissue samples are discussed. As the presence of neoplastic giant tumour cells is an index for a poor prognosis in human medicine, not only the entity of the tumour must be named, but also the exact significance of the giant cell type:, e.g. fibrosarcoma with osteoclast-like giant cells, hepatic carcinoma with reactive giant cells, malignant seminoma with neoplastic giant cells, angiosarcoma with both neoplastic giant cells and osteoclast-like giant cells. This would enable the classification of further neoplasias dealing with clinical courses of the diseases. Over the past years our stains have remained stable. It is possible to carry out retrospective investigations with archived tissue samples and make permanent preparations. A reclassification and a refined form of diagnosis (tumour and giant cell type) would be recommended.
A Giant Cell Tumor of the Sacrum or a Soft Tissue Giant Cell Tumor?
AbstractSTUDY DESIGN: A case report. OBJECTIVE: Giant cell tumors are rare primary bone tumors. Generally, these tumors are expanding osteolytic lesions, but soft tissue giant cell tumors can occur. This is a case report of an unusual incidence of a giant cell tumor within the spinal sacral canal, in which there was no involvement of the surrounding bone or ligament structures and that was signaled by radicular pain. The pathologic course of the tumor is described. SUMMARY OF BACKGROUND DATA: A 24-year-old woman had monoradicular pain in the right leg in the region of S2. Neuroradiologic examination showed a mass within the sacral spinal canal compromising the right S2 root, with no sign of bone involvement. METHODS: A sacral laminectomy was performed. A tumor was located entirely intraspinally and extradurally and was removed completely. A giant cell tumor was identified in histologic examination. RESULT: The patient recovered completely. No local regrowth or metastasis occurred during a 20-month follow-up. CONCLUSION: The treatment of choice in giant cell tumors is complete surgical resection. Radiotherapy is recommended in cases of subtotal resection. Careful follow-up is warranted, because recurrence and metastasis are not uncommon.
Journal of Modern Oncology · 2020 · 3 citations · open access
Polyploid giant cancer cells and their role in the formation of resistance to therapeutic treatment
AbstractThe review considers the properties of polyploid giant tumor cells a new target for the development of cancer therapy. Various number of polyploid giant tumor cells are detected in almost all human solid tumors. Their number increases under the influence of hypoxia, radiation, and after chemotherapy. Previously, these cells were not considered to be worth studying as they do not proliferate and eventually die as a result of one of the cell death mechanisms action. Recent data have demonstrated that polyploid giant cells can give rise to daughter cells that possess tumorigenicity and are characterized as stem tumor cells. Giant tumor cells and daughter cells are involved in the processes of metastasis, recurrence, drug resistance formation and radio-resistance of tumors. The search is under way for molecular targets that could prevent the appearance or contribute to the elimination of previously formed polyploid giant tumor cells. The combination of traditional therapy that causes the death of proliferating tumor cells and allows their elimination, with the use of tools that could prevent the appearance of resistant polyploid giant cells and their daughter cells, can be the key to the effective treatment of malignancies.
Medical Entomology and Zoology · 1997 · 0 citations
佛教漢梵大辭典 = Buddhist Chinese-Sanskrit dictionary
AbstractPolyploidy is a conserved mechanism in cell development and stress responses. Multiple stresses of treatment, including radiation and chemotherapy drugs, can induce the polyploidization of tumor cells. Through endoreplication or cell fusion, diploid tumor cells convert into giant tumor cells with single large nuclei or multiple small nucleuses. Some of the stress-induced colossal cells, which were previously thought to be senescent and have no ability to proliferate, can escape the fate of death by a special way. They can remain alive at least before producing progeny cells through asymmetric cell division, a depolyploidization way named neosis. Those large and danger cells are recognized as polyploid giant cancer cells (PGCCs). Such cells are under suspicion of being highly related to tumor recurrence and metastasis after treatment and can bring new targets for cancer therapy. However, differences in formation mechanisms between PGCCs and well-accepted polyploid cancer cells are largely unknown. In this review, the methods used in different studies to induce polyploid cells are summarized, and several mechanisms of polyploidization are demonstrated. Besides, we discuss some characteristics related to the poor prognosis caused by PGCCs in order to provide readers with a more comprehensive understanding of these huge cells.
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.
DeCure is a research and publication project, not medical advice and not a treatment. "DeCure for X" describes a research goal, not a claim that a cure exists. Backing a cure is a contribution to fund the research — it is not an investment, and confers no yield, royalty, equity or IP ownership. Papers are published open-access by the DeCure.ai DAO.
