Figure 5 from Small-Molecule Polθ Inhibitors Provide Safe and Effective Tumor Radiosensitization in Preclinical Models
<p>Polθ inhibitor ART899 combined with radiation causes significant tumor growth delay <i>in vivo</i> and is well tolerated. <b>A,</b> ART899 plasma concentration following oral dosage of ART899 at 50 or 150 mg/kg. Mouse plasma samples (<i>n</i> = 3 per trea...
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2025
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| _version_ | 1849927633248190464 |
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| author | Gonzalo Rodriguez-Berriguete (15056057) |
| author2 | Marco Ranzani (15056060) Remko Prevo (15056063) Rathi Puliyadi (15056066) Nicole Machado (15056069) Hannah R. Bolland (15056072) Val Millar (15056075) Daniel Ebner (15056078) Marie Boursier (15056081) Aurora Cerutti (15056084) Alessandro Cicconi (15056087) Alessandro Galbiati (15056090) Diego Grande (15056093) Vera Grinkevich (15056096) Jayesh B. Majithiya (15056099) Desiree Piscitello (15056102) Eeson Rajendra (15056105) Martin L. Stockley (15056108) Simon J. Boulton (15056111) Ester M. Hammond (15056114) Robert A. Heald (15056117) Graeme C.M. Smith (15056120) Helen M.R. Robinson (15056123) Geoff S. Higgins (15056126) |
| author2_role | author author author author author author author author author author author author author author author author author author author author author author author |
| author_facet | Gonzalo Rodriguez-Berriguete (15056057) Marco Ranzani (15056060) Remko Prevo (15056063) Rathi Puliyadi (15056066) Nicole Machado (15056069) Hannah R. Bolland (15056072) Val Millar (15056075) Daniel Ebner (15056078) Marie Boursier (15056081) Aurora Cerutti (15056084) Alessandro Cicconi (15056087) Alessandro Galbiati (15056090) Diego Grande (15056093) Vera Grinkevich (15056096) Jayesh B. Majithiya (15056099) Desiree Piscitello (15056102) Eeson Rajendra (15056105) Martin L. Stockley (15056108) Simon J. Boulton (15056111) Ester M. Hammond (15056114) Robert A. Heald (15056117) Graeme C.M. Smith (15056120) Helen M.R. Robinson (15056123) Geoff S. Higgins (15056126) |
| author_role | author |
| dc.creator.none.fl_str_mv | Gonzalo Rodriguez-Berriguete (15056057) Marco Ranzani (15056060) Remko Prevo (15056063) Rathi Puliyadi (15056066) Nicole Machado (15056069) Hannah R. Bolland (15056072) Val Millar (15056075) Daniel Ebner (15056078) Marie Boursier (15056081) Aurora Cerutti (15056084) Alessandro Cicconi (15056087) Alessandro Galbiati (15056090) Diego Grande (15056093) Vera Grinkevich (15056096) Jayesh B. Majithiya (15056099) Desiree Piscitello (15056102) Eeson Rajendra (15056105) Martin L. Stockley (15056108) Simon J. Boulton (15056111) Ester M. Hammond (15056114) Robert A. Heald (15056117) Graeme C.M. Smith (15056120) Helen M.R. Robinson (15056123) Geoff S. Higgins (15056126) |
| dc.date.none.fl_str_mv | 2025-11-25T13:07:56Z |
| dc.identifier.none.fl_str_mv | 10.1158/1078-0432.30707632 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/figure/Figure_5_from_Small-Molecule_Pol_Inhibitors_Provide_Safe_and_Effective_Tumor_Radiosensitization_in_Preclinical_Models/30707632 |
| dc.rights.none.fl_str_mv | CC BY info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Cancer Molecular and Cellular Biology Therapeutic Research and Development DNA Damage and Repair DNA repair Radiation Oncology Molecular targets of radiation response Small Molecule Agents |
| dc.title.none.fl_str_mv | Figure 5 from Small-Molecule Polθ Inhibitors Provide Safe and Effective Tumor Radiosensitization in Preclinical Models |
| dc.type.none.fl_str_mv | Image Figure info:eu-repo/semantics/publishedVersion image |
| description | <p>Polθ inhibitor ART899 combined with radiation causes significant tumor growth delay <i>in vivo</i> and is well tolerated. <b>A,</b> ART899 plasma concentration following oral dosage of ART899 at 50 or 150 mg/kg. Mouse plasma samples (<i>n</i> = 3 per treatment group) were collected at 30 minutes, 1, 2, 4, 8, and 12 hours after last dose. <b>B–E,</b> HCT116 tumor-bearing mice treated with 150 mg/kg Polθ inhibitor ART899 twice daily for 12 days and/or 10 × 2 Gy (days 1–5 and 8–12). Vehicle (<i>n</i> = 9); ART899 (<i>n</i> = 10); 10 × 2 Gy + vehicle (<i>n</i> = 10); 10 × 2 Gy + ART899 (<i>n</i> = 10). <b>B,</b> Mean ± SEM relative tumor size. <i>P</i> value from mixed effect model and Dunnett post-test. Comparison of tumor size at the latest common timepoint for 10 × 2 Gy versus 10 × 2 Gy + ART899 are shown in Supplementary Fig. S6A. <b>C,</b> Individual mouse graphs. <b>D,</b> Kaplan–Meier plot for a tumor size threshold of 1,000 mm<sup>3</sup>. HR: Hazard ratio (hazard rate of IR arm / hazard rate of IR + ART899 arm); <i>P</i> value from the log-rank (Mantel-Cox) test comparing IR alone and IR + ART558. The median time to a tumor size of 1,000 mm<sup>3</sup> for the IR + ART899 arm versus the IR arm and the corresponding ratio are shown in Supplementary Fig. S6B. <b>E,</b> Average mouse weight ± SD from all treatment groups over time. Individual mouse weights are shown in Supplementary Fig. S6C.</p> |
| eu_rights_str_mv | openAccess |
| id | Manara_314bf4df6d6ebffd41ce5cd12bf41477 |
| identifier_str_mv | 10.1158/1078-0432.30707632 |
| network_acronym_str | Manara |
| network_name_str | ManaraRepo |
| oai_identifier_str | oai:figshare.com:article/30707632 |
| publishDate | 2025 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY |
| spelling | Figure 5 from Small-Molecule Polθ Inhibitors Provide Safe and Effective Tumor Radiosensitization in Preclinical ModelsGonzalo Rodriguez-Berriguete (15056057)Marco Ranzani (15056060)Remko Prevo (15056063)Rathi Puliyadi (15056066)Nicole Machado (15056069)Hannah R. Bolland (15056072)Val Millar (15056075)Daniel Ebner (15056078)Marie Boursier (15056081)Aurora Cerutti (15056084)Alessandro Cicconi (15056087)Alessandro Galbiati (15056090)Diego Grande (15056093)Vera Grinkevich (15056096)Jayesh B. Majithiya (15056099)Desiree Piscitello (15056102)Eeson Rajendra (15056105)Martin L. Stockley (15056108)Simon J. Boulton (15056111)Ester M. Hammond (15056114)Robert A. Heald (15056117)Graeme C.M. Smith (15056120)Helen M.R. Robinson (15056123)Geoff S. Higgins (15056126)CancerMolecular and Cellular BiologyTherapeutic Research and DevelopmentDNA Damage and RepairDNA repairRadiation OncologyMolecular targets of radiation responseSmall Molecule Agents<p>Polθ inhibitor ART899 combined with radiation causes significant tumor growth delay <i>in vivo</i> and is well tolerated. <b>A,</b> ART899 plasma concentration following oral dosage of ART899 at 50 or 150 mg/kg. Mouse plasma samples (<i>n</i> = 3 per treatment group) were collected at 30 minutes, 1, 2, 4, 8, and 12 hours after last dose. <b>B–E,</b> HCT116 tumor-bearing mice treated with 150 mg/kg Polθ inhibitor ART899 twice daily for 12 days and/or 10 × 2 Gy (days 1–5 and 8–12). Vehicle (<i>n</i> = 9); ART899 (<i>n</i> = 10); 10 × 2 Gy + vehicle (<i>n</i> = 10); 10 × 2 Gy + ART899 (<i>n</i> = 10). <b>B,</b> Mean ± SEM relative tumor size. <i>P</i> value from mixed effect model and Dunnett post-test. Comparison of tumor size at the latest common timepoint for 10 × 2 Gy versus 10 × 2 Gy + ART899 are shown in Supplementary Fig. S6A. <b>C,</b> Individual mouse graphs. <b>D,</b> Kaplan–Meier plot for a tumor size threshold of 1,000 mm<sup>3</sup>. HR: Hazard ratio (hazard rate of IR arm / hazard rate of IR + ART899 arm); <i>P</i> value from the log-rank (Mantel-Cox) test comparing IR alone and IR + ART558. The median time to a tumor size of 1,000 mm<sup>3</sup> for the IR + ART899 arm versus the IR arm and the corresponding ratio are shown in Supplementary Fig. S6B. <b>E,</b> Average mouse weight ± SD from all treatment groups over time. Individual mouse weights are shown in Supplementary Fig. S6C.</p>2025-11-25T13:07:56ZImageFigureinfo:eu-repo/semantics/publishedVersionimage10.1158/1078-0432.30707632https://figshare.com/articles/figure/Figure_5_from_Small-Molecule_Pol_Inhibitors_Provide_Safe_and_Effective_Tumor_Radiosensitization_in_Preclinical_Models/30707632CC BYinfo:eu-repo/semantics/openAccessoai:figshare.com:article/307076322025-11-25T13:07:56Z |
| spellingShingle | Figure 5 from Small-Molecule Polθ Inhibitors Provide Safe and Effective Tumor Radiosensitization in Preclinical Models Gonzalo Rodriguez-Berriguete (15056057) Cancer Molecular and Cellular Biology Therapeutic Research and Development DNA Damage and Repair DNA repair Radiation Oncology Molecular targets of radiation response Small Molecule Agents |
| status_str | publishedVersion |
| title | Figure 5 from Small-Molecule Polθ Inhibitors Provide Safe and Effective Tumor Radiosensitization in Preclinical Models |
| title_full | Figure 5 from Small-Molecule Polθ Inhibitors Provide Safe and Effective Tumor Radiosensitization in Preclinical Models |
| title_fullStr | Figure 5 from Small-Molecule Polθ Inhibitors Provide Safe and Effective Tumor Radiosensitization in Preclinical Models |
| title_full_unstemmed | Figure 5 from Small-Molecule Polθ Inhibitors Provide Safe and Effective Tumor Radiosensitization in Preclinical Models |
| title_short | Figure 5 from Small-Molecule Polθ Inhibitors Provide Safe and Effective Tumor Radiosensitization in Preclinical Models |
| title_sort | Figure 5 from Small-Molecule Polθ Inhibitors Provide Safe and Effective Tumor Radiosensitization in Preclinical Models |
| topic | Cancer Molecular and Cellular Biology Therapeutic Research and Development DNA Damage and Repair DNA repair Radiation Oncology Molecular targets of radiation response Small Molecule Agents |