Other experimental therapies for glioma. Westphal M, Lamszus K.
Recent Results Cancer Res. 2009;171:155-64.
Department of Neurosurgery,
University Hospital Hamburg Eppendorf, Martinistrasse 52, Hamburg 20251,
Germany. westphal@plexus.uke.uni-hamburg.de
Experimental therapies for
glioma are mostly based on the insights into the cell biology of the tumors
studied by modern methods including genomics and metabolomics. In surgery,
intraoperative visualization of residual tumor by fluorescence has helped with
the radicality of resection. Although temozolamide has become an important agent
in the combined radiochemotherapy of newly diagnosed glioblastoma, understanding
the underlying mechanisms of action and resistance has led to alterations in
dosing schemes, which may be more beneficial than the introduction of new
agents. Targeted therapies that have been highly promising in other solid tumors
have been rather disappointing in gliomas, not for the lack of promising targets
but most likely due to inefficacy of the reagents to reach their target. Direct
delivery of reagents with interstitial infusion via convection-enhanced delivery
has proven to be safe and effective, but the potential of that technology has
not been exploited because many technicalities are still to be worked out, and
better, more selective reagents are needed. Gene therapy has been reactivated
with direct adeno-viral application to transfer HSV-Tk into tumor cells by
adenoviral vectors, still awaiting final analysis. Oncolytic viruses are also
under long-term refinement and await definitive pivotal clinical trials.
Immunotherapy is currently focusing on vaccination strategies using either
specifically pulsed dendritic cells or immunization with a specific peptide,
which is unique to the vIII variant of the epidemal growth factor receptor. An
area attracting immense attention for basic research as well as translation into
clinical use is the characterization of neural stem cells and their theraputic
potential when appropriately manipulated.In general, there is a wide spectrum of
specific neuro-oncological therapy developments, which are not only extrapolated
from general oncology but also based on translational research in the field of
glioma biology.