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Volume 2 Issue 2, February 2021
News & Views
The complexity of glioblastoma is becoming increasingly recognized. Three recent studies used single-cell approaches that integrate cellular states, transcriptional trajectories, and metabolic alterations to uncover multiple dimensions of cellular and molecular heterogeneity and provide a framework for additional functional investigation and therapeutic development.
Metabolic reprogramming mediates resistance to therapy and rewires cancer-cell-signaling networks, paving the way to the discovery of enhanced treatment strategies through acquired vulnerabilities. A study now points to lipotoxicity dependent on Raf-1 kinase that occurs after activation of the liver receptor LXRα as a therapeutic intervention for the treatment of hepatocellular carcinoma.
Pathway-based classification of glioblastoma uncovers a mitochondrial subtype with therapeutic vulnerabilities
Garofano et al. use single-cell RNA-sequencing data to classify glioblastomas along a metabolic axis of mitochondrial and glycolytic/plurimetabolic states and a neurodevelopmental axis of proliferative/progenitor and neuronal states.
Gradient of Developmental and Injury Response transcriptional states defines functional vulnerabilities underpinning glioblastoma heterogeneity
Pugh and colleagues use single-cell RNA sequencing, CRISPR screens and functional assays to define a gradient of developmental and wound-response cell states in glioblastoma stem cells, revealing insights into glioblastoma origins and potential therapeutic targets.
Piccolo and colleagues perform integrated single-cell analyses and identify YAP/TAZ regulation of glioma stem cell differentiation as a core dependency for tumor maintenance.
Targeting glutamine dependence through GLS1 inhibition suppresses ARID1A-inactivated clear cell ovarian carcinoma
Zhang and colleagues report that targeting GLS1 alleviates the glutamine dependence of ARID1A-mutated ovarian clear cell carcinomas, thereby suppressing their growth.
Zender, Dauch and colleagues demonstrate that pharmacologically induced lipotoxicity by activating LXRα and Raf-1 inhibition provides a metabolic therapeutic strategy for hepatocellular carcinoma.
Complement activation promoted by the lectin pathway mediates C3aR-dependent sarcoma progression and immunosuppression
Magrini et. al. study sarcoma development and antitumor immune response in complement-deficient murine hosts, demonstrating a role for the C3a–C3aR axis in promoting immunosuppressive macrophages.
Few-shot learning creates predictive models of drug response that translate from high-throughput screens to individual patients
Ma et al. apply few-shot learning to train a neural network model on cell-line drug-response data, and they subsequently transfer it to distinct biological contexts including different tissues and patient-derived tumor cells and xenografts.