GlioblastomaGlioblastoma MultiformeMultiforme: The Terminator: The TerminatorEric C. Holland, PNAS 2000Eric C. Holland, PNAS 2000

MedUniMedUni Vienna at the international forefront in the study of brain Vienna at the international forefront in the study of brain tumourstumours

In In Austria around 1,700 primary brain Austria around 1,700 primary brain tumourstumours are newly diagnosed each year. The most are newly diagnosed each year. The most common form of primary brain common form of primary brain tumourtumour in adults is the in adults is the glioblastomaglioblastoma, for which a , for which a standard therapy used worldwide was able to be established in 20standard therapy used worldwide was able to be established in 2005 with the 05 with the involvement of involvement of MedUniMedUni Vienna.Vienna. With the introduction of this wellWith the introduction of this well--tolerated therapy the tolerated therapy the number of patients who are still alive two years after the diagnnumber of patients who are still alive two years after the diagnosis has been able to osis has been able to increase from 10% to 26%. increase from 10% to 26%. This therapy is used for 18This therapy is used for 18--65 year65 year--olds and consists of an olds and consists of an operation on the operation on the tumourtumour tissue, most of which can be removed, and subsequent sixtissue, most of which can be removed, and subsequent six--week combined radiation and chemotherapy followed by chemotherapweek combined radiation and chemotherapy followed by chemotherapy over six months. y over six months. The chemotherapy is in tablet form, which generally means that oThe chemotherapy is in tablet form, which generally means that outpatient therapy is utpatient therapy is possible.possible.At the ASCO a study has now been presented involving Univ. At the ASCO a study has now been presented involving Univ. Prof.inProf.in Dr.inDr.in Christine Christine Marosi, Department of Medicine I, and Univ. Marosi, Department of Medicine I, and Univ. Prof.inProf.in Dr.inDr.in Karin Karin DieckmannDieckmann, Department , Department of Radiotherapy, which shows that in the age group of patients oof Radiotherapy, which shows that in the age group of patients over 60 years old it is no ver 60 years old it is no worse to have less stressful twoworse to have less stressful two--week radiation therapy or solely chemotherapy than week radiation therapy or solely chemotherapy than long radiation therapy.long radiation therapy. So for older patients the stressful long radiation therapy overSo for older patients the stressful long radiation therapy over six six weeks is no longer necessary. weeks is no longer necessary. These latest study findings are therefore highly relevant These latest study findings are therefore highly relevant for daily for daily neuroneuro--oncologicaloncological practice.practice.

Two other studies at Two other studies at MedUniMedUni Vienna are currently dealing with the possibility of Vienna are currently dealing with the possibility of vaccination against brain vaccination against brain tumourstumours and the and the antiangiogenesisantiangiogenesis, , i.e. the inhibition of i.e. the inhibition of vascularisationvascularisation using medication to cut off the supply of nutrients to the using medication to cut off the supply of nutrients to the tumourstumours. This . This procedure seems to be very effective with malignant brain procedure seems to be very effective with malignant brain tumourstumours and may lead to a and may lead to a further increase in "longfurther increase in "long--term survivors".term survivors".

SeizuresSeizures (general(general--partial)partial)NeurologicalNeurological deficitsdeficitsCognitiveCognitive dysfunctiondysfunctionRaised inracranial pressure:Raised inracranial pressure:

headache, nausea, vomitting, drowsinessheadache, nausea, vomitting, drowsiness

MultiformeMultiforme SymptomsSymptoms

MultiformeMultiforme MorphologyMorphology

Behin et al, The Lancet 2003Behin et al, The Lancet 2003

MultiformeMultiforme HistologyHistology

Eric C. Holland, PNAS 2000Eric C. Holland, PNAS 2000Behin et al, The Lancet 2003Behin et al, The Lancet 2003

MultiformeMultiforme CellsCells--ofof--OriginOrigin

A A2B5E EGFF FGFG GFAPM MBPN NestinO O4P PDGR

Cell SignalingCell Signaling

MultiformeMultiforme Altered SignalingAltered Signaling

Altered TranslationAltered Translation

Cell CycleCell Cycle

Altered Cell CycleAltered Cell Cycle

Benefit of Epigenetic MGMT-Silencing(O6-methylguanine-DNA methyltransferase)

GlioblastomaGlioblastoma MultiformeMultiforme: : NovelNovel therapytherapy strategiesstrategies

•• ViralViral vectorvector lysis, transferlysis, transferof of lethallethal genesgenes

•• Immun Immun responseresponsemodificationmodification

•• Mouse Mouse modelsmodels

NovelNovel therapytherapy strategies:strategies:Herpes simplex Virus TK/GCV paradigmHerpes simplex Virus TK/GCV paradigm

NovelNovel therapytherapy strategies:strategies:Oncolytic AdenovirusOncolytic Adenovirus

NovelNovel therapytherapy strategies:strategies:HVJ (Sendaivirus) HVJ (Sendaivirus) -- liposomesliposomes

Mouse model of GBMMouse model of GBM

Multiple signaling pathways altered in GBM tumors modulate the DDR. Genes with copy-number loss and/or inactivating mutations or copy-number gain and/or activating mutations

are presented in green or red, respectively.

Squatrito M , and Holland E C Cancer Res 2011;71:5945-5949

©2011 by American Association for Cancer Research