Glioblastoma multiforme tedavisindeki birincil engel: Kan beyin bariyeri

Emine Yazıcı; Aleyna Gezen; Ece Oylumlu; Gamze Tanrıöver

doi:10.19161/etd.1621826

EN TR

The primary obstacle in glioblastoma multiforme treatment: The blood-brain barrier

Abstract

Classified as grade IV astrocytoma by the World Health Organization, Glioblastoma Multiforme (GBM) is the most aggressive and common primary brain tumor of the central nervous system. The current standard treatment for GBM patients in clinical practice involves resection followed by concurrent radiotherapy and chemotherapy. The effectiveness of these approaches in GBM treatment remains limited due to factors such as tumor heterogeneity, glioma stem cells, DNA damage repair mechanisms, and the blood-brain barrier. Temozolomide, due to its lipophilic nature, easily crosses the blood-brain barrier, making it an effective agent in the treatment of gliomas. However, a significant proportion of patients experience recurrence, and due to prolonged exposure to temozolomide, they develop resistance to the treatment. There is currently no alternative therapeutic approach for recurrent GBM patients. Therefore, the investigation of novel agents is of paramount importance to prolong patient survival. The permeability of the blood-brain barrier to therapeutic agents in the treatment of brain tumors exhibits heterogeneity. Consequently, various strategies aimed at modulating this barrier permeability to enhance drug bioavailability should be developed. Overcoming the blood-brain barrier is a critical consideration in targeted therapeutic approaches and must be addressed in the development of effective treatments. This review aims to provide a comprehensive analysis of the relationship between the blood-brain barrier and GBM, presenting the most recent findings and insights on the subject.

Keywords

Glioblastoma multiforme tedavisindeki birincil engel: Kan beyin bariyeri

Öz

Dünya Sağlık Örgütü tarafından derece 4 astrositom olarak sınıflandırılan Glioblastoma Multiforme (GBM), merkezi sinir sisteminin en agresif ve yaygın görülen primer beyin tümörüdür. Klinikteki GBM hastaları için mevcut tedavi; rezeksiyonun ardından eş zamanlı uygulanan radyoterapi ve kemoterapiyi içermektedir. GBM tedavisindeki bu yaklaşımların etkinliği; tümör heterojenliği, glioma kök hücreleri, DNA hasar onarım mekanizmaları ve kan-beyin bariyeri gibi faktörler nedeniyle yetersiz kalmaktadır. Temozolomid, lipofilik bir ajan olması nedeniyle kan-beyin bariyerini kolaylıkla geçebilmekte ve bu özelliği sayesinde glioma tedavisinde etkili bir ajan olarak kullanılmaktadır. Bununla birlikte, hastaların büyük bir kısmında nüks meydana gelmekte ve bu hastalar temozolomide uzun süre maruz kaldığı için tedaviye direnç geliştirmektedir. Günümüzde, nüks eden GBM hastaları için farklı bir tedavi yaklaşımı söz konusu değildir. Bu yüzden, hasta sağkalımını uzatacak yeni ajanların araştırılması son derece önemlidir. Terapötik ajanların merkezi sinir sistemine iletimi, kan-beyin bariyeri tarafından engellenmekte ve beyindeki hedeflenen bölgelere erişim, GBM için yeni ilaçların geliştirilmesinde en büyük zorluklardan birini oluşturmaktadır. Beyin tümörleri tedavisinde kan-beyin bariyerinin ilaç geçirgenliği heterojen bir yapı sergilemektedir. Sonuç olarak, bu bariyer geçirgenliğinin modüle edilmesi ve ilaç biyoyararlanımını artırmayı hedefleyen çeşitli stratejiler geliştirilmelidir. Kan-beyin bariyerinin aşılması, hedefe yönelik tedavi yaklaşımlarında dikkate alınması gereken önemli bir konudur. Bu derleme, kan-beyin bariyerinin GBM ile ilişkisini inceleyerek, konuya dair güncel bilgileri ayrıntılı bir şekilde sunmayı amaçlamaktadır

Anahtar Kelimeler

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Details

Primary Language

Turkish

Subjects

Brain and Nerve Surgery (Neurosurgery) , Cancer Cell Biology

Journal Section

Review

Authors

Emine Yazıcı ^*
0009-0009-7320-5764
Türkiye

Aleyna Gezen
0009-0001-2753-274X
Türkiye

Ece Oylumlu
0000-0003-4234-9086
Türkiye

Gamze Tanrıöver
0000-0002-8002-5544
Türkiye

Publication Date

March 12, 2025

Submission Date

January 16, 2025

Acceptance Date

January 31, 2025

Published in Issue

Year 2025 Volume: 64 Number: 1

DOI

https://doi.org/10.19161/etd.1621826

IZ

https://izlik.org/JA95FB89DF

Cite

RIS / Bibtex

Vancouver

1.Emine Yazıcı, Aleyna Gezen, Ece Oylumlu, Gamze Tanrıöver. Glioblastoma multiforme tedavisindeki birincil engel: Kan beyin bariyeri. EJM. 2025 Mar. 1;64(1):184-92. doi:10.19161/etd.1621826