A Drug Screening Pipeline Using 2D and 3D Patient-Derived In Vitro Models for Pre-Clinical Analysis of Therapy Response in Glioblastoma
| Autor: | Lisa M. Ebert, Sakthi Lenin, Santosh Poonnoose, Ulrich Baumgartner, Stuart M. Pitson, Melinda N Tea, Erica C. F. Yeo, Kaitlin G. Scheer, Guillermo A. Gomez, Elise Ponthier, Rebecca J. Ormsby, Bryan W. Day, Mariana Oksdath Mansilla |
|---|---|
| Přispěvatelé: | Lenin, Sakthi, Ponthier, Elise, Scheer, Kaitlin G., Yeo, Erica C.F., Tea, Melinda N., Ebert, Lisa M., Mansilla, Mariana Oksdath, Poonnoose, Santosh, Baumgartner, Ulrich, Day, Bryan W., Ormsby, Rebecca J., Pitson, Stuart M., Gomez, Guillermo A. |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
therapy resistance
QH301-705.5 medicine.medical_treatment Brain tumor Drug Evaluation Preclinical Antineoplastic Agents Catalysis Article Inorganic Chemistry Glioma medicine Humans tumor microenvironment drug screening Physical and Theoretical Chemistry Precision Medicine Biology (General) Molecular Biology QD1-999 Spectroscopy Cells Cultured organoids Chemotherapy Tumor microenvironment business.industry Brain Neoplasms Organic Chemistry glioblastoma General Medicine personalized medicine medicine.disease Primary tumor Computer Science Applications Radiation therapy Chemistry Cancer cell Cancer research Stem cell business |
| Zdroj: | International Journal of Molecular Sciences, Vol 22, Iss 4322, p 4322 (2021) International Journal of Molecular Sciences Volume 22 Issue 9 |
| ISSN: | 1661-6596 1422-0067 |
| Popis: | Glioblastoma is one of the most common and lethal types of primary brain tumor. Despite aggressive treatment with chemotherapy and radiotherapy, tumor recurrence within 6–9 months is common. To overcome this, more effective therapies targeting cancer cell stemness, invasion, metabolism, cell death resistance and the interactions of tumor cells with their surrounding microen-vironment are required. In this study, we performed a systematic review of the molecular mechanisms that drive glioblastoma progression, which led to the identification of 65 drugs/inhibitors that we screened for their efficacy to kill patient-derived glioma stem cells in two dimensional (2D) cul-tures and patient-derived three dimensional (3D) glioblastoma explant organoids (GBOs). From the screening, we found a group of drugs that presented different selectivity on different patient-derived in vitro models. Moreover, we found that Costunolide, a TERT inhibitor, was effective in reducing the cell viability in vitro of both primary tumor models as well as tumor models pre-treated with chemotherapy and radiotherapy. These results present a novel workflow for screening a relatively large groups of drugs, whose results could lead to the identification of more personalized and effective treatment for recurrent glioblastoma Refereed/Peer-reviewed |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|