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Development
Of Novel Targeted Therapies In The Treatment Of Malignant Glioma
Jeremy N. Rich
& Darell D. Bigner
Preface.
Malignant gliomas are highly lethal tumours despite maximal therapy.
Traditional treatments for these cancers — which rely on nonspecific,
cytotoxic approaches that generally act through damaging DNA — have a marginal
impact on patient survival.
However, advances in the understanding of the molecular biology underlying
glioma pathogenesis have revealed abnormalities in a set of common cellular
pathways and functions among the majority of these tumours that are now being
targeted by novel agents in preclinical and clinical development.
Such molecularly targeted agents might offer the promise of improved tumour
control without substantial toxicity.
Still, significant challenges in their development remain: the inability to
predict tumour response and limitations of drug delivery into the tumour.
Two essential aspects of glioma therapy remain to be achieved: local control of
the primary tumour and blockade of tumour-cell invasion of normal brain.
Summary.
Gliomas
are strikingly heterogeneous tumours in terms of their pathology and gene
expression, even within a single tumour.
But
despite this variability, common alterations within specific cellular signal
transduction pathways or cellular functions can be found in most malignant
gliomas, some of which represent opportunities for therapeutic intervention.
This
article focuses on molecularly targeted therapies for malignant glioma, in
particular, those aimed at growth factor receptors (including the epidermal
growth factor receptor, the vascular endothelial growth factor receptor and the
platelet-derived growth factor receptor), the RAS/RAF/MAPK/ERK pathway and
mammalian target of rapamycin.
Clinical
trial results so far are presented, and key issues in the clinical development
of these therapies are discussed, including drug delivery, monitoring of
activity and the use of drug combinations.
© 2004 Nature Publishing Group
Source:
http://www.nature.com/cgi-taf/DynaPage.taf?file=/nrd/journal/v3/n5/abs/nrd1380_fs.html&dynoptions=doi1090069400
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