ArticleCancer chemotherapy and pharmacology2020
Prospective use of the single-mouse experimental design for the evaluation of PLX038A.
Article in Cancer chemotherapy and pharmacology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
14 citing papers in PubMed, 19 citations in OpenAlex.
- Article
- Targeting DNA Topoisomerase I for the Treatment of Cancer: Past, Present and Future.Journal of molecular biology · 2026Review
- Could a Long-Acting Prodrug of SN-38 be Efficacious in Sacituzumab Govitecan-Resistant Tumors?BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2024Article
- Contemporary preclinical mouse models for pediatric rhabdomyosarcoma: from bedside to bench to bedside.Frontiers in oncology · 2024Article
- Evaluating preclinical evidence for clinical translation in childhood brain tumours: Guidelines from the CONNECT, PNOC, and ITCC brain networks.Frontiers in oncology · 2023Article
- PLX038: A Long-Acting Topoisomerase I Inhibitor With Robust Antitumor Activity in ATM-Deficient Tumors and Potent Synergy With PARP Inhibitors.Molecular cancer therapeutics · 2022Article
- Evaluation of Hedgehog Pathway Inhibitors as a Therapeutic Option for Uterine Leiomyosarcoma Using the Xenograft Model.Reproductive sciences (Thousand Oaks, Calif.) · 2022Article
- PEGylated talazoparib enhances therapeutic window of its combination with temozolomide in Ewing sarcoma.iScience · 2022Article
- Approaches to identifying drug resistance mechanisms to clinically relevant treatments in childhood rhabdomyosarcoma.Cancer drug resistance (Alhambra, Calif.) · 2022Article
- The B7-H3-Targeting Antibody-Drug Conjugate m276-SL-PBD Is Potently Effective Against Pediatric Cancer Preclinical Solid Tumor Models.Clinical cancer research : an official journal of the American Association for Cancer Research · 2021Article
- Preclinical In Vivo Modeling of Pediatric Sarcoma-Promises and Limitations.Journal of clinical medicine · 2021Review
- Prioritization of Novel Agents for Patients with Rhabdomyosarcoma: A Report from the Children's Oncology Group (COG) New Agents for Rhabdomyosarcoma Task Force.Journal of clinical medicine · 2021Review
- Phenotypic profiling with a living biobank of primary rhabdomyosarcoma unravels disease heterogeneity and AKT sensitivity.Nature communications · 2020Article
- Cancer Stem Cells Decide the Fate of Cancer Immunotherapy by Remodeling Tumor Microenvironment.Cancer control : journal of the Moffitt Cancer CenterReview
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
purposeDefining robust criteria for drug activity in preclinical studies allows for fewer animals per treatment group, and potentially allows for inclusion of additional cancer models that more accurately represent genetic diversity and, potentially, allows for tumor sensitivity biomarker identification.
methodsUsing a single-mouse design, 32 pediatric xenograft tumor models representing diverse pediatric cancer types [Ewing sarcoma (9), brain (4), rhabdomyosarcoma (10), Wilms tumor (4), and non-CNS rhabdoid tumors (5)] were evaluated for response to a single administration of pegylated-SN38 (PLX038A), a controlled-release PEGylated formulation of SN-38. Endpoints measured were percent tumor regression, and event-free survival (EFS). The correlation between response to PLX038A was compared to that for ten models treated with irinotecan (2.5 mg/kg × 5 days × 2 cycles), using a traditional design (10 mice/group). Correlations between tumor sensitivity, genetic mutations and gene expression were sought. Models showing no disease at week 20 were categorized as 'extreme responders' to PLX038A, whereas those with EFS less than 5 weeks were categorized as 'resistant'.
resultsThe activity of PLX038A was evaluable in 31/32 models. PLX038A induced > 50% volume regressions in 25 models (78%). Initial tumor volume regression correlated only modestly with EFS (r
conclusionsThis study demonstrates the feasibility of using a single-mouse design for assessing the antitumor activity of an agent, while encompassing greater genetic diversity representative of childhood cancers. PLX038A was highly active in most xenograft models, and tumor sensitivity to PLX038A was correlated with sensitivity to irinotecan, validating the single-mouse design in identifying agents with the same mechanism of action. Biomarkers that correlated with model sensitivity included wild-type TP53, or mutant TP53 but with a mutation in 53BP1, thus a defect in DNA damage response. These results support the value of the single-mouse experimental design.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.