{
  "abstract": "Purpose: Uveal melanoma (UM) is a rare but aggressive intraocular malignancy originating in the uvea (choroid, iris, and ciliary body). Despite primary treatment, 50% of UM patients develop metastases to the liver, lungs, bones, and skin. Topotecan, a topoisomerase I inhibitor, and SP141, an MDM2 inhibitor, have been studied in cancers, including retinoblastoma. This study explores a combined approach with these drugs in the 92-1 UM cell line. Methods: Primary choroidal melanoma-derived 92-1 cells were treated with topotecan and SP141 individually to determine IC50 values. Cell viability and proliferation were assessed using the MTT assay and the xCELLigence real-time monitoring system. The synergistic effects were analyzed quantitatively using the Loewe Additivity and Highest Single-Agent (HSA) models. Flow cytometry was employed to analyze cell cycle distribution, while cell death and apoptosis were monitored via high-throughput, real-time quantitative analysis using the IncuCyte live-cell kinetic imaging system. Results: Both Topotecan and SP141 induced significant cell death in 92-1 cells. xCELLigence showed dose- and time-dependent inhibition of proliferation. Combining sub-IC50 concentrations of topotecan and SP141 exhibited significant synergistic effects, markedly reducing growth. Cell cycle analysis revealed that topotecan causes a dose-dependent biphasic arrest in G2 and S phases, while SP141 causes G2/M arrest, leading to cell death. Cytotoxicity assays corroborated increased cell death following combination therapy, and the Caspase 3/7 assay indicated that apoptosis is the mechanism underlying cell death. Conclusions: The multi-targeted approach combining topotecan and SP141 drugs demonstrated synergistic therapeutic effects in 92-1 cells, suggesting a potential treatment strategy for managing UM.",
  "abstract_shown": true,
  "affiliations": [
    "Medical College of Wisconsin"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 8,
  "authors": [
    {
      "name": "A. Thomas"
    },
    {
      "name": "U. R. Addi"
    },
    {
      "name": "A. Wu"
    },
    {
      "name": "K. Kozak"
    },
    {
      "name": "R. Collery"
    },
    {
      "name": "A. F. Joshi"
    },
    {
      "name": "A. Ramasubramanian"
    },
    {
      "affs": [
        0
      ],
      "name": "S. S. Chaurasia"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/f9wjdtg3btbkg.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.23.753860",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.23.753860v1.full",
  "id": "f9wjdtg3btbkg",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.09.23.753860v1",
  "language": null,
  "licence": "CC-BY-ND",
  "licence_label": "CC BY-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "cancer biology"
    ],
    [
      "openalex",
      "2731|Ocular Oncology and Treatments"
    ]
  ],
  "openalex": "W7214171110",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.23.753860v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-23",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/f9wjdtg3btbkg.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:24:15Z",
      "native_id": "10.64898/2026.09.23.753860",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.23.753860v1"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "biorxiv:cancer biology",
      "subfield": "oncology"
    }
  ],
  "title": "Topotecan Syndergizes with SP141 in the Management of Uveal Melanoma",
  "title_text": "Topotecan Syndergizes with SP141 in the Management of Uveal Melanoma",
  "type": "preprint",
  "updated_at": "2026-10-30T12:24:15Z",
  "url": "https://research.draconitic.com/paper/f9wjdtg3btbkg",
  "venue": "bioRxiv",
  "versions": []
}