Highlights of This Issue

Death receptor present on the plasma membrane of cancer cells can be activated by chemical compounds to induce cell apoptosis. Shih and his colleagues developed the one-bead two-compound (OB2C) ultra-high throughput screening method for the discovery of synthetic death ligands against cancer cells. They discovered LLS2, a novel galectin-1 inhibitor that can kill a variety of cancer cells. They also found LLS2 exhibits synergistic activity with paclitaxel in vitro and in vivo. These results indicated that OB2C combinatorial technology is a highly efficient drug-screening platform and LLS2 discovered through this method can be further optimized for anti-cancer drug development.

Indole-based tambjamine analogues is a new group of potent anion transporters. In this study, Manuel-Manresa, Korrodi-Gregório and colleagues demonstrated the mechanism of these novel natural-derived tambjamine analogues in lung cancer cells. Treatment of Indole-based tambjamine analogues resulted in dysregulation of BCL2 and BIRC5/surviving genes which suggested the apoptotic pathway induction demonstrated by pro-apoptotic markers and by a decrease towards the pro-survival members of the Bcl-2 proteins. This apoptosis might be activated by the p38 MAPK through ROS cellular stress induction. Significant therapeutic effect of these compounds was observed in subcutaneous and orthotopic lung cancer mice models indicating a good potential for clinical development.

Tissue biopsy analysis of genomic alterations is the standard of care for molecular profiling. Circulating tumor DNA (ctDNA) biopsies detect alterations in blood, non-invasively. Chae, Davis and colleagues report high overall concordance in paired tissue and ctDNA biopsies, but relatively low concordance when mutations were detected (excluding wild type/wild type genes). Mutations with high allele frequently were more likely to be concordant. Importantly, over half of mutations detected using each platform were not detected in the other technique. These results highlight the potential need to use both tissue and blood biopsies to understand the complex biology of breast cancer.

Patient derived xenografts (PDXs) in colorectal cancer (CRC) are robust preclinical models, essential for drug discovery. While multiple factors (tumor source, grade, stage, acquisition strategy, genotype, time to implantation, and prior therapy) have been assumed to affect PDX engraftment, they have not been systematically studied. Here, using 90 CRC patient specimens subcutaneously implanted into immunodeficient mice (50 established PDXs), Katsiampoura, Raghav and colleagues found that tissue acquisition strategy (surgery vs. biopsy) was the only key determinant for successful PDX engraftment. These findings contrast with current notions and can help streamline PDX modelling protocols allowing for pervasive integration in CRC translational research.