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Toward Deciphering the Mechanisms of Chemoresistance in Human Glioblastoma

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The prognosis of patients with glioblastoma (GBM) is extremely poor. Temozolomide (TMZ) is the only drug that has been shown to significantly enhance survival in GBM patients. However, the therapeutic benefit of this drug is limited by resistance, mainly regulated by O6-Methylguanine-DNA-methyltransferase ...

The prognosis of patients with glioblastoma (GBM) is extremely poor. Temozolomide (TMZ) is the only drug that has been shown to significantly enhance survival in GBM patients. However, the therapeutic benefit of this drug is limited by resistance, mainly regulated by O6-Methylguanine-DNA-methyltransferase (MGMT) protein. The MGMT gene is silenced by promoter hypermethylation in approximately 40% of GBM and this is associated with a markedly better overall survival in patients treated with TMZ. However, it is not known as to why all GBM patients, even those with favorable low or undetectable levels of MGMT, fail to respond to TMZ therapy. It is likely that the TMZ response in GBM is limited by secondary resistance of which the principal mechanisms are poorly known. There are several published results from elegantly conducted investigations focused on better understanding of the mechanisms and how to overcome the emergence TMZ resistance. Together, these results and those from the ongoing work investigating the underpinning mechanisms of TMZ resistance will facilitate our strategies of developing novel therapies aimed at thwarting the emergence of resistance in GBM patients. In this Frontiers Research Topic, we propose to create a research forum for reporting and discussing the findings from such efforts.


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