Summary

CORNETO is a new computational tool that helps researchers combine different types of biological data with prior biological knowledge to map how molecules like genes and proteins interact inside cells.

By analysing different samples together at once, CORNETO shows which biological processes are common and which are unique across cell types and conditions. 

Researchers have used CORNETO to reveal shared and cell-specific pathways in disease research, e.g. to identify signalling pathways associated with chemotherapy resistance in ovarian cancer patients.

Results of a study led by VHIO’s Prostate Cancer Group suggest that treatment with CDK4/6 inhibitors followed by senloytic therapies and PARP inhibitors could improve outcomes and combat cancer drug resistance in advanced prostate cancer.

The application of CAR-T cell therapy against solid tumors is often hindered by the dense and rigid tumor extracellular matrix (ECM). While combining CAR-T with hyaluronidase (HAase) to reduce ECM is apparent, the efficacy is limited because of low accumulation and penetration efficiency of HAase inside the tumor tissue. Herein, the stimuli-responsive HAase-loaded nanogels (H-NGs) which are conjugated on the surface of CAR-T cells were designed for synergistically improving HAase accumulation, ECM degradation and CAR-T cell efficacy. The conjugation of H-NGs on the T cell surface was achieved through metabolic oligosaccharide engineering (MOE) in a semi-quantitatively controlled manner. Intravenous injection of H-NGs armed CAR-T cells resulted in more ECM degradation than co-injection of CAR-T cells and free H-NGs, leading to an 83.2% tumor inhibition rate and relieves tumor suppressive microenvironment in the Raji solid tumor model. Proteomic analysis of the harvested tumor tissues indicated that the combining of H-NGs and CAR-T cell collaboratively reduces cell adhesion and enhanced leukocyte transendothelial migration. Overall, this work simultaneously boosts the efficacy of hyaluronidase and CAR-T cells in combating solid tumor, which has broad application potential in cancer combination therapy.