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. 2013 Nov 25;6(12):1475-506.
doi: 10.3390/ph6121475.

Glioblastoma multiforme therapy and mechanisms of resistance

Yulian P Ramirez  1 , Jessica L Weatherbee, Richard T Wheelhouse, Alonzo H Ross
Affiliations

Glioblastoma multiforme therapy and mechanisms of resistance

Yulian P Ramirez et al. Pharmaceuticals (Basel). .

Abstract

Glioblastoma multiforme (GBM) is a grade IV brain tumor characterized by a heterogeneous population of cells that are highly infiltrative, angiogenic and resistant to chemotherapy. The current standard of care, comprised of surgical resection followed by radiation and the chemotherapeutic agent temozolomide, only provides patients with a 12-14 month survival period post-diagnosis. Long-term survival for GBM patients remains uncommon as cells with intrinsic or acquired resistance to treatment repopulate the tumor. In this review we will describe the mechanisms of resistance, and how they may be overcome to improve the survival of GBM patients by implementing novel chemotherapy drugs, new drug combinations and new approaches relating to DNA damage, angiogenesis and autophagy.

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Figures

Scheme 1
Scheme 1
Prodrug activation of temozolomide.
Scheme 2
Scheme 2
Biological fate of methyldiazonium ions.
Scheme 3
Scheme 3
Mechanism of prodrug activation and action of carmustine.
Scheme 4
Scheme 4
Mechanism of action of MGMT and structures of the two clinically tested MGMT inactivators.
Figure 1
Figure 1
Novel TMZ-like drugs.
Scheme 5
Scheme 5
Reaction of DP86 in phosphate buffer pD = 7.4. * Sites of 13C labelling.
See this image and copyright information in PMC

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