A neurocentric perspective on glioma invasion

Abstract

Malignant gliomas are devastating tumours that frequently kill patients within 1 year of diagnosis. The major obstacle to a cure is diffuse invasion, which enables tumours to escape complete surgical resection and chemo- and radiation therapy. Gliomas use the same tortuous extracellular routes of migration that are travelled by immature neurons and stem cells, frequently using blood vessels as guides. They repurpose ion channels to dynamically adjust their cell volume to accommodate to narrow spaces and breach the blood-brain barrier through disruption of astrocytic endfeet, which envelop blood vessels. The unique biology of glioma invasion provides hitherto unexplored brain-specific therapeutic targets for this devastating disease.

A frightening thought: Neuronal activity enhances tumor growth

“…The finding that neuronal activity promotes the growth of brain tumors using the same synaptic signaling molecules involved in normal synaptic development is entirely unexpected. However, the paper expands on a recent argument that gliomas must be examined from a more "neurocentric" perspective -in the context of the many interactions of the tumor with the surrounding brain tissue rather than merely a cancerous growth within the skull [7]. This realization is also supported by studies suggesting that glioma is a neurodegenerative disease [8,9].…”

Pharmacological inhibition of lipid droplet formation enhances the effectiveness of curcumin in glioblastoma

“…Glioblastoma multiforme is a highly aggressive and drugresistant type of brain cancer which currently lacks effective treatments [30,31]. Temozolomide, a DNA methylating agent, is the first-line drug used in concomitant and adjuvant radiochemotherapy against glioblastoma [32][33][34].…”

Long-term exposure to irinotecan reduces cell migration in glioma cells

“…This suggests that the prolonged exposure to irinotecan or etoposide does not result in the emergence of a cell population better able to respond to oxidative stress. 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 One of the hallmarks of glioma is local invasion [5,7] , and it was therefore of interest to determine [24]. For Col3A1, the C6-Ir cell line showed a significantly reduced gene expression compared to the C6-Et and C6-V cell line ( Figure 5D), and for Col1A2 C6-Ir also showed reduced gene expression compared to the C6-Et ( Figure 5E).…”

“…Despite testing a multitude of chemotherapy agents and strategies, very little progress has been made in extending the life expectancy of those diagnosed with a GBM, since the establishment of the Stupp protocol (a combination of radiotherapy and temozolomide) a decade ago [2,3]. This is believed to be due to a high level of intrinsic drug resistance [4] combined with the fact that these tumours tend to diffusely invade the local brain parenchyma making it difficult to identify the perimeter and effectively remove them surgically [5][6][7]. An improvement in clinical outcome therefore requires identification of drugs that can inhibit invasion as well as promote cell death.…”