Targeting the Molecular Circuitry Underlying Glioblastoma Invasion
Pp. 264-281 (18)
Sean M. Lawless, Johnny C. Akers, Chun-Lin Chen, Rui Liu, Bob Carter and Clark C. Chen
Glioblastoma is the most common form of primary brain tumor. It remains
one of the deadliest of human cancers. Despite work by dedicated clinicians and
scientists over the past forty years, the median survival of the afflicted patients remains
approximately 12-14 months.
A major challenge in the treatment of glioblastoma involves its inherently infiltrative
and invasive properties. The tendency for the glioblastoma cells to microscopically
extend beyond the region of gross anatomic abnormality renders complete surgical
resection impossible. Further, glioblastoma infiltration into regions of the cerebrum
where the blood-brain-barrier remains intact increases the probability of therapeutic
failure. In these contexts, understanding the molecular mechanisms underlying the
invasive nature of glioblastoma cells may afford opportunities for meaningful
One of the central principles that emerged from the past decades of cancer research is
that cancer cells subvert molecular circuitry inherent with the cell of origin. As differing
aspects of these circuits are manifested during normal development, it comes as no
surprise that the patterns of glioblastoma migration and invasion are highly reminiscent
of those observed in astrocytes during development. These highly coordinated processes
include establishment of cell polarity, directional cellular adhesion to the extracellular
matrix, cytoskeletal rearrangement, and asymmetric detachment to the extracellular
matrix. Our understanding of the factors that mediate these cues have led to novel
This chapter will highlight our current understanding of the signaling pathways that
mediate glioblastoma chemotaxis with special focus on pharmacologic inhibitors
available for therapeutic interventions.
Chemotaxis, brain tumor, CD44, cadherin, integrin,
metalloproteinases, receptor tyrosine kinase, inhibitors/therapeutics.
Center for Theoretical and Applied Neuro-Oncology, Moores Cancer Center, Division of Neurosurgery, University of California, San Diego Health System, La Jolla, California, CA 92093, USA.