Academic Journal
Treatment-driven selection of chemoresistant Ewing sarcoma tumors with limited drug distribution
| العنوان: | Treatment-driven selection of chemoresistant Ewing sarcoma tumors with limited drug distribution |
|---|---|
| المؤلفون: | Castillo-Écija, Helena, Monterrubio, Carles, Pascual-Pasto, Guillem, Gómez, Soledad, García-Domínguez, D. J., Hontecillas-Prieto, Lourdes, Resa-Pares, Claudia, Burgueño, Víctor, Paco, Sonia, Olaciregui, Nagore G., Vila-Ubach, Mónica, Restrepo-Perdomo, Camilo, Cuadrado-Vilanova, María, Balaguer-Lluna, Leire, Pérez-Jaume, Sara, Castañeda, Alicia, Santamaría, Vicente, Roldán, Mónica, Suñol, Mariona, Álava, Enrique de, Mora, Jaume, Lavarino, Cinzia, Carcaboso, Ángel M. |
| المساهمون: | Fundación Científica Asociación Española Contra el Cáncer, European Commission, Instituto de Salud Carlos III, Centro de Investigación Biomédica en Red Cáncer (España), Asociación Pablo Ugarte, Fundación María García Estrada, Ministerio de Economía y Competitividad (España), Fundación BBVA |
| بيانات النشر: | Elsevier |
| سنة النشر: | 2020 |
| المجموعة: | Digital.CSIC (Consejo Superior de Investigaciones Científicas / Spanish National Research Council) |
| مصطلحات موضوعية: | Intratumor drug distribution, SN-38/irinotecan, Drug resistance, Cancer evolution, Tumor microdialysis, Ewing sarcoma |
| الوصف: | Ewing sarcoma is a bone and soft tissue tumor predominantly affecting adolescents and young adults. To characterize changes in anticancer drug activity and intratumor drug distribution during the evolution of Ewing sarcomas, we used immunodeficient mice to establish pairs of patient-derived xenografts (PDX) at early (initial diagnosis) and late (relapse or refractory progression) stages of the disease from three patients. Analysis of copy number alterations (CNA) in early passage PDX tissues showed that two tumor pairs established from patients which responded initially to therapy and relapsed more than one year later displayed similar CNAs at early and late stages. For these two patients, PDX established from late tumors were more resistant to chemotherapy (irinotecan) than early counterparts. In contrast, the tumor pair established at refractory progression showed highly dissimilar CNA profiles, and the pattern of response to chemotherapy was discordant with those of relapsed cases. In mice receiving irinotecan infusions, the level of SN-38 (active metabolite of irinotecan) in the intracellular tumor compartment was reduced in tumors at later stages compared to earlier tumors for those pairs bearing similar CNAs, suggesting that distribution of anticancer drug shifted toward the extracellular compartment during clonal tumor evolution. Overexpression of the drug transporter P-glycoprotein in late tumor was likely responsible for this shift in drug distribution in one of the cases. ; The work at Hospital Sant Joan de Deu was supported by associations of parents and families of children with cancer. The work of EdA was supported by the AECC Scientific Foundation (GCB13-1578), ISCIII-FEDER (PI14/01466 and PI17/00464), CIBERONC (CB16/12/00361), Asociación Pablo Ugarte and Fundación María García Estrada. The work of JM was supported by the AECC Scientific Foundation (GCB13-1578) and Asociación Pablo Ugarte. The work of AMC was supported by grants from the AECC Scientific Foundation, MINECO (SAF2011-22660), Fundacion ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | unknown |
| تدمد: | 0168-3659 |
| Relation: | #PLACEHOLDER_PARENT_METADATA_VALUE#; info:eu-repo/grantAgreement/EC/FP7/276998; http://doi.org/10.1016/j.jconrel.2020.05.032; Sí; e-issn: 1873-4995; Journal of controlled release : official journal of the Controlled Release Society 324: 440-449 (2020); http://hdl.handle.net/10261/236226; http://dx.doi.org/10.13039/501100003329; http://dx.doi.org/10.13039/501100002704; http://dx.doi.org/10.13039/501100004587; http://dx.doi.org/10.13039/100007406; http://dx.doi.org/10.13039/501100000780; http://dx.doi.org/10.13039/501100008545 |
| DOI: | 10.1016/j.jconrel.2020.05.032 |
| DOI: | 10.13039/501100003329 |
| DOI: | 10.13039/501100002704 |
| DOI: | 10.13039/501100004587 |
| DOI: | 10.13039/100007406 |
| DOI: | 10.13039/501100000780 |
| DOI: | 10.13039/501100008545 |
| الاتاحة: | http://hdl.handle.net/10261/236226 https://doi.org/10.1016/j.jconrel.2020.05.032 https://doi.org/10.13039/501100003329 https://doi.org/10.13039/501100002704 https://doi.org/10.13039/501100004587 https://doi.org/10.13039/100007406 https://doi.org/10.13039/501100000780 https://doi.org/10.13039/501100008545 |
| Rights: | none |
| رقم الانضمام: | edsbas.24AA2B00 |
| قاعدة البيانات: | BASE |
| تدمد: | 01683659 |
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| DOI: | 10.1016/j.jconrel.2020.05.032 |