Chemoresistant Glioblastoma
Invited conference paper presented and published in conference proceedings


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AbstractGlioblastoma is the most malignant brain tumour in adults. Temozolomide, as a standard of care,is current the only effective chemotherapeutic with moderate survival benefit. However, intrinsic and acquired temozolomide resistances represent it main deficiencies in clinical application. MGMT mediate DNA repair is accepted as the major reason of temozolomide resistance. Promoter methylation status of MGMT provides a useful prognostic marker but no meaningful therapeutic approaches yet. In addition, studies on MMR, BER, multidrug resistance and cancer specific pathways have supplemented from different aspects to the current theory. Further characterization on temozolomide resistance mechanism will help to discover new targets for future glioblastoma treatment. Cancer stem cell (CSC) theory is also used in explaining therapeutic resistance. Dedifferentiation of glioma cells to glioma stem cells (GSCs) under chemo stress partially explained the reason of acquired temozolomide resistance (ATR). Studies on CSC specific signallings have demonstrated that hedgehog (Hh)/Gli1 signalling pathway play a central role in regulating GSC behaviour and therapeutic resistance, and is dependent on the activation of IGF signalling. Our preliminary studies on glioblastoma cell line (U87) based ATR also showed an upregulation in IGF signalling. Interestingly, we found that IGF2, rather than IGF1 as previous reported, was overexpressed in our ATR model. Inhibition of IGF2 enhanced the cytotoxic effect of temozolomide in ATR cells. We further investigate the IGF2 expression pattern in TMZ sensitive, resistant and paired samples from glioblastoma patients at their first diagnosis and relapse. No significant difference was found between primary sensitive patients and primary resistant patients in either tissue or serum level. Paired samples showed some interesting IGF2 expression changes pattern at glioblastoma recurrence.
Acceptance Date21/09/2018
All Author(s) ListPOON Wai Sang
Name of Conference14th Asia Oceanian Skull Base Societies Congress
Start Date of Conference21/09/2018
End Date of Conference23/09/2018
Place of ConferenceTaichung
Country/Region of ConferenceTaiwan
Proceedings TitlePreliminary Congress Program: 14th Asia-Oceanian Skull Base Societies Congress
Year2018
LanguagesEnglish-United Kingdom
KeywordsChemoresistant Glioblastoma

Last updated on 2019-09-12 at 15:48