Gliobastoma multiforme (GBM) is an aggressive malignant form of brain tumour for which effective therapies are limited. Genetically engineered mouse models (GEMMs) harbouring mutations in components of the main signalling pathways that are altered in human GBM – including the receptor tyrosine kinase (RTK)–RAS– phosphoinositide-3-kinase (PI3K) pathway – are available. However, these GEMMs display a long latency to tumorigenesis and advanced tumour heterogeneity, which represents a challenge in preclinical drug testing. In this study, Zoë Weaver Ohler and colleagues developed an orthotopic and tractable mouse model of GBM by transplanting brain tumour cells derived from GBM-GEMMs into the brain (orthotopically) of syngeneic mice (non-transgenic wild-type mice with identical genetic backgrounds and intact immune systems). This model develops GBM with features of the human disease, including high vascularisation and aggressive invasion of surrounding tissues, and thus was used to test the effects of two drugs that are currently in clinical trials for GBM and other solid tumours, namely BKM120 and PD0325901 [inhibitors of PI3K and mitogen-activated protein kinase (MAPK), respectively]. When tested in vitro and in vivo as single agents, neither drug improved mouse survival. However, combination therapy increased cancer cell apoptosis, decreased tumour cell proliferation and enhanced survival, owing to a synergistic effect of the drugs on suppression of the PI3K pathway (which regulates cell proliferation and survival). Therefore, this model represents a valuable preclinical system for advancing current therapies and for testing novel drugs and drug combinations against GBM. Page 45
A preclinical model of glioblastoma
A preclinical model of glioblastoma. Dis Model Mech 1 January 2015; 8 (1): e0102. doi:
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DMM Journal Meeting 2023: Infectious Diseases Through an Evolutionary Lens
We are delighted to announce that our 2023 Journal Meeting ‘Infectious Diseases Through an Evolutionary Lens’ will be held from 17-19 October 2023 in London, UK. Registration is open now.
New drugs to squash the spread of malaria
In this Research Article, the Baum lab identify a new class of antimalarials to block Plasmodium gamete formation. This article has been highlighted as our Editor’s Choice, and you can find out more in our interview with first author Sabrina Yahiya.
preLights 5th Birthday webinar
preLights, our preprint highlighting service, is celebrating its 5th birthday this year. To mark the occasion, join us online on 14 March 2023 at 16:00 GMT for a discussion, led by four preLights alumni, on how to identify and navigate the challenges and opportunities while shaping your career as an early-career researcher.
Sex, obesity and melanoma
Emily Montal et al. develop a zebrafish model to investigate the effect of genetic- and diet-induced obesity, as well as sex, on melanoma initiation and progression. Their findings, summarised in this Editor’s Choice article, suggest that melanoma initiation is dependent on both sex and obesity.
Apply for a DMM Conference Travel Grant
DMM Conference Travel Grants support early-career researchers wanting to attend in-person and virtual meetings. Find out when the next application deadline is and hear from past recipients about their experience.
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