Glioblastoma (GBM) remains one of the most intransigent of cancers, with a median overall survival of only 15 months after diagnosis. Drug treatments have largely proven ineffective; it is thought that this is related to the heterogeneous nature and plasticity of GBM-initiating stem cell lineages. Although many combination drug therapies are being positioned to address tumour heterogeneity, the most promising therapeutic approaches for GBM to date appear to be those targeting GBM by vaccination or antibody- and cell-based immunotherapy. We review the most recent clinical trials for GBM and discuss the role of adaptive clinical trials in developing personalised treatment strategies to address intra- and inter-tumoral heterogeneity.

It is more effective to maintain good health than to regain it after losing it. This work focuses on the biochemical defense mechanisms against free radicals and their role in building and maintaining antioxidant shields, aiming to show how to balance, as much as possible, the situations in which we are exposed to free radicals. To achieve this aim, foods, fruits, and marine algae with a high antioxidant content should constitute the basis of nutritional elements, since natural products are known to have significantly greater assimilation efficiency. This review also gives the perspective in which the use of antioxidants can extend the life of food products, by protecting them from damage caused by oxidation as well as their use as food additives.

Personalized cancer treatments using combinations of drugs with a synergistic effect is attractive but proves to be highly challenging. Here we present an approach to uncover the efficacy of drug combinations based on the analysis of mono-drug effects. For this we used dose-response data from pharmacogenomic encyclopedias and represent these as a drug atlas. The drug atlas represents the relations between drug effects and allows to identify independent processes for which the tumor might be particularly vulnerable when attacked by two drugs. Our approach enables the prediction of combination-therapy which can be linked to tumor-driving mutations. By using this strategy, we can uncover potential effective drug combinations on a pan-cancer scale. Predicted synergies are provided and have been validated in glioblastoma, breast cancer, melanoma and leukemia mouse-models, resulting in therapeutic synergy in 75% of the tested models. This indicates that we can accurately predict effective drug combinations with translational value.

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.