Cargando…

Targeted c-Myc Inhibition and Systemic Temozolomide Therapy Extend Survival in Glioblastoma Xenografts

Glioblastoma is a highly aggressive disease with poor patient outcomes despite current treatment options, which consist of surgery, radiation, and chemotherapy. However, these strategies present challenges such as resistance development, damage to healthy tissue, and complications due to the blood–b...

Descripción completa

Detalles Bibliográficos
Autores principales: Dhungel, Laxmi, Harris, Cayla, Romine, Lauren, Sarkaria, Jan, Raucher, Drazen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10294868/
https://www.ncbi.nlm.nih.gov/pubmed/37370649
http://dx.doi.org/10.3390/bioengineering10060718
_version_ 1785063285110865920
author Dhungel, Laxmi
Harris, Cayla
Romine, Lauren
Sarkaria, Jan
Raucher, Drazen
author_facet Dhungel, Laxmi
Harris, Cayla
Romine, Lauren
Sarkaria, Jan
Raucher, Drazen
author_sort Dhungel, Laxmi
collection PubMed
description Glioblastoma is a highly aggressive disease with poor patient outcomes despite current treatment options, which consist of surgery, radiation, and chemotherapy. However, these strategies present challenges such as resistance development, damage to healthy tissue, and complications due to the blood–brain barrier. There is therefore a critical need for new treatment modalities that can selectively target tumor cells, minimize resistance development, and improve patient survival. Temozolomide is the current standard chemotherapeutic agent for glioblastoma, yet its use is hindered by drug resistance and severe side effects. Combination therapy using multiple drugs acting synergistically to kill cancer cells and with multiple targets can provide increased efficacy at lower drug concentrations and reduce side effects. In our previous work, we designed a therapeutic peptide (Bac-ELP1-H1) targeting the c-myc oncogene and demonstrated its ability to reduce tumor size, delay neurological deficits, and improve survival in a rat glioblastoma model. In this study, we expanded our research to the U87 glioblastoma cell line and investigated the efficacy of Bac-ELP1-H1/hyperthermia treatment, as well as the combination treatment of temozolomide and Bac-ELP1-H1, in suppressing tumor growth and extending survival in athymic mice. Our experiments revealed that the combination treatment of Bac-ELP1-H1 and temozolomide acted synergistically to enhance survival in mice and was more effective in reducing tumor progression than the single components. Additionally, our study demonstrated the effectiveness of hyperthermia in facilitating the accumulation of the Bac-ELP1-H1 protein at the tumor site. Our findings suggest that the combination of targeted c-myc inhibitory biopolymer with systemic temozolomide therapy may represent a promising alternative treatment option for glioblastoma patients.
format Online
Article
Text
id pubmed-10294868
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-102948682023-06-28 Targeted c-Myc Inhibition and Systemic Temozolomide Therapy Extend Survival in Glioblastoma Xenografts Dhungel, Laxmi Harris, Cayla Romine, Lauren Sarkaria, Jan Raucher, Drazen Bioengineering (Basel) Article Glioblastoma is a highly aggressive disease with poor patient outcomes despite current treatment options, which consist of surgery, radiation, and chemotherapy. However, these strategies present challenges such as resistance development, damage to healthy tissue, and complications due to the blood–brain barrier. There is therefore a critical need for new treatment modalities that can selectively target tumor cells, minimize resistance development, and improve patient survival. Temozolomide is the current standard chemotherapeutic agent for glioblastoma, yet its use is hindered by drug resistance and severe side effects. Combination therapy using multiple drugs acting synergistically to kill cancer cells and with multiple targets can provide increased efficacy at lower drug concentrations and reduce side effects. In our previous work, we designed a therapeutic peptide (Bac-ELP1-H1) targeting the c-myc oncogene and demonstrated its ability to reduce tumor size, delay neurological deficits, and improve survival in a rat glioblastoma model. In this study, we expanded our research to the U87 glioblastoma cell line and investigated the efficacy of Bac-ELP1-H1/hyperthermia treatment, as well as the combination treatment of temozolomide and Bac-ELP1-H1, in suppressing tumor growth and extending survival in athymic mice. Our experiments revealed that the combination treatment of Bac-ELP1-H1 and temozolomide acted synergistically to enhance survival in mice and was more effective in reducing tumor progression than the single components. Additionally, our study demonstrated the effectiveness of hyperthermia in facilitating the accumulation of the Bac-ELP1-H1 protein at the tumor site. Our findings suggest that the combination of targeted c-myc inhibitory biopolymer with systemic temozolomide therapy may represent a promising alternative treatment option for glioblastoma patients. MDPI 2023-06-14 /pmc/articles/PMC10294868/ /pubmed/37370649 http://dx.doi.org/10.3390/bioengineering10060718 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Dhungel, Laxmi
Harris, Cayla
Romine, Lauren
Sarkaria, Jan
Raucher, Drazen
Targeted c-Myc Inhibition and Systemic Temozolomide Therapy Extend Survival in Glioblastoma Xenografts
title Targeted c-Myc Inhibition and Systemic Temozolomide Therapy Extend Survival in Glioblastoma Xenografts
title_full Targeted c-Myc Inhibition and Systemic Temozolomide Therapy Extend Survival in Glioblastoma Xenografts
title_fullStr Targeted c-Myc Inhibition and Systemic Temozolomide Therapy Extend Survival in Glioblastoma Xenografts
title_full_unstemmed Targeted c-Myc Inhibition and Systemic Temozolomide Therapy Extend Survival in Glioblastoma Xenografts
title_short Targeted c-Myc Inhibition and Systemic Temozolomide Therapy Extend Survival in Glioblastoma Xenografts
title_sort targeted c-myc inhibition and systemic temozolomide therapy extend survival in glioblastoma xenografts
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10294868/
https://www.ncbi.nlm.nih.gov/pubmed/37370649
http://dx.doi.org/10.3390/bioengineering10060718
work_keys_str_mv AT dhungellaxmi targetedcmycinhibitionandsystemictemozolomidetherapyextendsurvivalinglioblastomaxenografts
AT harriscayla targetedcmycinhibitionandsystemictemozolomidetherapyextendsurvivalinglioblastomaxenografts
AT rominelauren targetedcmycinhibitionandsystemictemozolomidetherapyextendsurvivalinglioblastomaxenografts
AT sarkariajan targetedcmycinhibitionandsystemictemozolomidetherapyextendsurvivalinglioblastomaxenografts
AT raucherdrazen targetedcmycinhibitionandsystemictemozolomidetherapyextendsurvivalinglioblastomaxenografts