Akademik Veri Yönetim Sistemi
Khan I., Hatiboğlu M. A., Karaçam B.
Yükseköğretim Kurumları Destekli Proje, BAP Araştırma Projesi, 2021 - 2022
The introduction of temozolomide (TMZ) as part
of standard treatment for glioblastoma in addition to surgical resection and
radiotherapy has proven to be a milestone, but in several cases, the patient
prognosis remains poor. This can be due to the underlying drug resistance
mechanisms which lead to therapeutic failure of TMZ in glioblastoma patients.
The molecular mechanism of TMZ resistance remains to be fully understood. With
the growing understanding of cancer stem cells in glioblastomas, developmental
pathways like Hedgehog and Notch signaling have been implicated in drug
resistance. Although few early reports suggesting the role of Notch signaling
in chemo-resistance have started to emerge, the molecular mechanism of Notch
signaling in TMZ resistance in glioblastoma remains to be fully explored. Our
preliminary study confirmed the overexpression of activated Notch1 in
chemo-resistant U87 glioblastoma cell
line. Also, the inhibition of Notch1 using DAPT inhibitor enhanced the TMZ
sensitivity in chemo-resistant cells. Therefore, in the present study, we
hypothesize that gaining a better understanding of key molecular players,
specifically, microRNAs (miRNA) associated with the Notch signaling pathway
would prove pivotal in overcoming TMZ resistance in glioblastoma. For this
purpose, firstly we will select miRNAs using bioinformatics target prediction
tools. Later, we will investigate the expression pattern of selected miRNA in
chemo-resistant and Notch1 knockout chemo-resistant U87 model in-vitro and
in-vivo. This study could act as an adjunct in understanding the molecular
mechanism of TMZ resistance in glioblastoma and aid in defining new targeted
therapeutic strategies for chemo-resistance in glioblastoma.