Objective
Glioblastoma is the most aggressive form of brain
cancer in adults with overall survival of less than 2 years from diagnosis.
Glioblastoma, as many other solid malignancies, shows a very high degree
of
cellular heterogeneity, with emerging cell subpopulations displaying resistant
and infiltrative phenotypes. Although many exploratory drugs have shown promise
in pre-clinical testing, none has yet shown therapeutic utility in the clinic.
The failure of drugs in clinical trials is most likely due to the
rapid acquisition of drug resistance amongst
the malignant cell populations emerging from the tumour mass. Dissecting the
basis of drug resistance in these cell lineages is of extreme importance to
develop novel therapies.
IOTA is an early-stage glioblastoma drug discovery company. We have
produced the
Glioblastoma Drug Bank, which details all the drugs
known to be active in glioblastoma pre-clinical studies. Our poster describes this
tool linking it to a range of downstream applications which may help identify
new approaches to predict drug responsiveness within malignant glioblastoma
cell populations arising from patient tumours.
IOTA is part of the
WINDOW Consortium, funded by the
Brain Tumour Charity (UK), within which we have the responsibility of building
a network of expert clinical and academic teams to develop and distribute
glioblastoma diagnostics and therapeutics. At the same time, IOTA is actively
establishing collaborative relationships with pharma companies to compare,
contrast and prioritise the clinical use of existing exploratory drugs in
glioblastoma and other cancers.
IOTA Pharmaceuticals are collaborating with both the
Leeds
Institute of Cancer and Pathology (LICAP) and the Cell Phenotyping
group within the Stem Cell Hotel at the
Centre for Stem Cells and
Regenerative Medicine at King’s College in London. Hand-in-hand with
LICAP and King’s, IOTA will deploy its established proprietary portfolio of
drug discovery technologies within a chemical biology platform to develop new
drugs and diagnostics to treat glioblastoma and other diseases of unmet
clinical need.
Our poster describes our team's current platforms for glioblastoma drug
discovery, focusing on IOTA's Glioblastoma Drug Bank
1,
previous work using patient-derived glioblastoma cells and high content
screening by group members at King's
2, and the recent
discovery of compounds targeting HSPD1-dependent metabolic pathways using
chemical biology approaches at LICAP
3, placing these
developments within a framework for
personalised glioblastoma therapy
based on chemical biology as an evolution of our previous ideas for
phenotypic screening in cancer
4.
References
1GBM Drug Bank - a new resource for glioblastoma drug discovery and informatics
research. Svensson et al Neuro Oncol. 2018 doi:
10.1093/neuonc/noy122.
2A high-content small molecule screen identifies sensitivity of
glioblastoma stem cells to inhibition of polo-like kinase 1. Danovi et al PLoS One. 2013 doi:
10.1371/journal.pone.0077053.
3KHS101 disrupts energy metabolism in human glioblastoma cells and
reduces tumor growth in mice. Polson et al Sci Transl Med. 2018 doi: 10.1126/scitranslmed.aar2718.
4Phenotypic screening in cancer drug discovery - past, present and
future. Moffat et al Nat Rev Drug Discov. 2014 doi:10.1038/nrd4366.
