Combination of T-DM1 and platinum-based chemotherapy in patient-derived xenograft models of muscle-invasive bladder cancer
Objective(s): To assess the efficacy and safety of T-DM1, as an anti-HER2 antibody-drug conjugate (ADC), alone and in combination with two platinum-based chemotherapy regimens in patient-derived xenografts (PDXs) of muscle-invasive bladder cancer (MIBC) established in immunodeficient mice. Materials...
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| Format: | Article |
| Language: | English |
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Mashhad University of Medical Sciences
2022-07-01
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| Series: | Iranian Journal of Basic Medical Sciences |
| Subjects: | |
| Online Access: | https://ijbms.mums.ac.ir/article_20449_87d6a67779c06f4a5e633813764c61c6.pdf |
| _version_ | 1811335781597315072 |
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| author | Abolfazl Razzaghdoust Samad Muhammadnejad Mahmoud Parvin Bahram Mofid Masoumeh Zangeneh Abbas Basiri |
| author_facet | Abolfazl Razzaghdoust Samad Muhammadnejad Mahmoud Parvin Bahram Mofid Masoumeh Zangeneh Abbas Basiri |
| author_sort | Abolfazl Razzaghdoust |
| collection | DOAJ |
| description | Objective(s): To assess the efficacy and safety of T-DM1, as an anti-HER2 antibody-drug conjugate (ADC), alone and in combination with two platinum-based chemotherapy regimens in patient-derived xenografts (PDXs) of muscle-invasive bladder cancer (MIBC) established in immunodeficient mice. Materials and Methods: After treatment initiation, tumor size was measured twice a week. Percent of tumor growth inhibition (TGI) and tumor response rates were calculated as efficacy endpoints. To evaluate treatment toxicity, relative body weight (RBW) was calculated for each group. For comparison of TGIs between treatment groups, the Kruskal-Wallis test was used. Also, the significance of the overall response (OR) rate between placebo groups with treatment groups was analyzed using Fisher’s exact test. Immunohistochemistry and fluorescence in situ hybridization techniques were used to evaluate the level of HER2 expression.Results: Our data showed that T-DM1 alone induced a moderate antitumor activity. While chemotherapy regimens induced a slight TGI when administered alone, interestingly, they showed strong antitumor activity when administered combined with T-DM1. The OR rates were higher when T-DM1 was combined with chemotherapy regimens than T-DM1 alone. When compared with the placebo group, the OR rates of combination groups were statistically significant. Our data also showed that the administered dose of each drug was well tolerated in mice. Conclusion: The combination of T-DM1 and platinum-based chemotherapy may represent a new treatment option for bladder tumors with even low HER2 expression, and could also provide substantial novel insight into tackling the challenges of MIBC management. |
| first_indexed | 2024-04-13T17:30:06Z |
| format | Article |
| id | doaj.art-eca7cda5131f49818a5ebca59557a4f3 |
| institution | Directory Open Access Journal |
| issn | 2008-3866 2008-3874 |
| language | English |
| last_indexed | 2024-04-13T17:30:06Z |
| publishDate | 2022-07-01 |
| publisher | Mashhad University of Medical Sciences |
| record_format | Article |
| series | Iranian Journal of Basic Medical Sciences |
| spelling | doaj.art-eca7cda5131f49818a5ebca59557a4f32022-12-22T02:37:37ZengMashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-38662008-38742022-07-0125781682110.22038/ijbms.2022.63509.1400520449Combination of T-DM1 and platinum-based chemotherapy in patient-derived xenograft models of muscle-invasive bladder cancerAbolfazl Razzaghdoust0Samad Muhammadnejad1Mahmoud Parvin2Bahram Mofid3Masoumeh Zangeneh4Abbas Basiri5Urology and Nephrology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, IranGene Therapy Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, IranDepartment of Pathology, Labbafinejad Hospital, Shahid Beheshti University of Medical Sciences, Tehran, IranDepartment of Oncology, Shohada-e-Tajrish Medical Center, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, IranTaleghani Hospital, Shahid Beheshti University of Medical Sciences, Tehran, IranUrology and Nephrology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, IranObjective(s): To assess the efficacy and safety of T-DM1, as an anti-HER2 antibody-drug conjugate (ADC), alone and in combination with two platinum-based chemotherapy regimens in patient-derived xenografts (PDXs) of muscle-invasive bladder cancer (MIBC) established in immunodeficient mice. Materials and Methods: After treatment initiation, tumor size was measured twice a week. Percent of tumor growth inhibition (TGI) and tumor response rates were calculated as efficacy endpoints. To evaluate treatment toxicity, relative body weight (RBW) was calculated for each group. For comparison of TGIs between treatment groups, the Kruskal-Wallis test was used. Also, the significance of the overall response (OR) rate between placebo groups with treatment groups was analyzed using Fisher’s exact test. Immunohistochemistry and fluorescence in situ hybridization techniques were used to evaluate the level of HER2 expression.Results: Our data showed that T-DM1 alone induced a moderate antitumor activity. While chemotherapy regimens induced a slight TGI when administered alone, interestingly, they showed strong antitumor activity when administered combined with T-DM1. The OR rates were higher when T-DM1 was combined with chemotherapy regimens than T-DM1 alone. When compared with the placebo group, the OR rates of combination groups were statistically significant. Our data also showed that the administered dose of each drug was well tolerated in mice. Conclusion: The combination of T-DM1 and platinum-based chemotherapy may represent a new treatment option for bladder tumors with even low HER2 expression, and could also provide substantial novel insight into tackling the challenges of MIBC management.https://ijbms.mums.ac.ir/article_20449_87d6a67779c06f4a5e633813764c61c6.pdfbladder cancerchemotherapypatient-derived xenografttargeted therapyt-dm1 |
| spellingShingle | Abolfazl Razzaghdoust Samad Muhammadnejad Mahmoud Parvin Bahram Mofid Masoumeh Zangeneh Abbas Basiri Combination of T-DM1 and platinum-based chemotherapy in patient-derived xenograft models of muscle-invasive bladder cancer Iranian Journal of Basic Medical Sciences bladder cancer chemotherapy patient-derived xenograft targeted therapy t-dm1 |
| title | Combination of T-DM1 and platinum-based chemotherapy in patient-derived xenograft models of muscle-invasive bladder cancer |
| title_full | Combination of T-DM1 and platinum-based chemotherapy in patient-derived xenograft models of muscle-invasive bladder cancer |
| title_fullStr | Combination of T-DM1 and platinum-based chemotherapy in patient-derived xenograft models of muscle-invasive bladder cancer |
| title_full_unstemmed | Combination of T-DM1 and platinum-based chemotherapy in patient-derived xenograft models of muscle-invasive bladder cancer |
| title_short | Combination of T-DM1 and platinum-based chemotherapy in patient-derived xenograft models of muscle-invasive bladder cancer |
| title_sort | combination of t dm1 and platinum based chemotherapy in patient derived xenograft models of muscle invasive bladder cancer |
| topic | bladder cancer chemotherapy patient-derived xenograft targeted therapy t-dm1 |
| url | https://ijbms.mums.ac.ir/article_20449_87d6a67779c06f4a5e633813764c61c6.pdf |
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