27.07.2020Transcriptomics-based Phenotypic Screening Supports Drug Discovery in Human Glioblastoma CellsIOTA releases a new paper on transcriptomics-based phenotypic screening by
Shapovalov et al. and is getting ready for product commercialization:
Glioblastoma (GBM) remains a particularly challenging cancer, with an aggressive phenotype and few promising treatment options. Future therapy will rely heavily on diagnosing and targeting aggressive GBM cellular phenotypes, both before and after drug treatment, as part of personalized therapy programs. Here, we use a genome-wide drug-induced gene expression (DIGEX) approach to define the cellular drug response phenotypes associated with two clinical drug candidates, the phosphodiesterase 10A inhibitor Mardepodect and the multi-kinase inhibitor Regorafenib. We identify genes encoding specific drug targets, some of which we validate as effective antiproliferative agents and combination therapies in human GBM cell models, including HMGCoA reductase (
HMGCR), salt-inducible kinase 1 (
SIK1), bradykinin receptor subtype B2 (
BDKRB2), and Janus kinase isoform 2 (
JAK2). Individual, personalized treatments will be essential if we are to address and overcome the pharmacological plasticity that GBM exhibits, and DIGEX will play a central role in validating future drugs, diagnostics, and possibly vaccine candidates for this challenging cancer.
READ MORE10.12.2020European Commission and Dealflow.eu selected IOTA Pharmaceuticals as one of the top 8 healthcare start-ups
Selection of start-ups was conducted together with EC's Innovation Radar and Horizon Result Platform. The competition is exceptionally interesting as all the companies have previously received significant non-dilutive EU grant funding. This funding has already allowed IOTA to develop sophisticated products and the following round of investment is needed for IOTA for market expansion and expansion of clinical network.
READ MORE18.09.2020Transcriptomics predicts compound synergy in drug and natural product treated glioblastoma cells Pathway analysis is an informative method for comparing and contrasting drug-induced gene expression in cellular systems. Here, we define the effects of the marine natural product fucoxanthin, separately and in combination with the prototypic phosphatidylinositol 3-kinase (PI3K) inhibitor LY-294002, on gene expression in a well-established human glioblastoma cell system, U87MG. Under conditions which inhibit cell proliferation, LY-294002 and fucoxanthin modulate many pathways in common, including the retinoblastoma, DNA damage, DNA replication and cell cycle pathways. In sharp contrast, we see profound differences in the expression of genes characteristic of pathways such as apoptosis and lipid metabolism, contributing to the development of a differentiated and distinctive drug-induced gene expression signature for each compound. Furthermore, in combination, fucoxanthin synergizes with LY-294002 in inhibiting the growth of U87MG cells, suggesting complementarity in their molecular modes of action and pointing to further treatment combinations. The synergy we observe between the dietary nutraceutical fucoxanthin and the synthetic chemical LY-294002 in producing growth arrest in glioblastoma, illustrates the potential of nutri-pharmaceutical combinations in targeting this challenging disease.
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