Volume 1 Issue 3, March 2020

Although many metabolic dependencies of cancer cells are well documented, altered cancer metabolism has not always been considered an active driver of tumorigenesis. Restrictive glutamine availability is now shown to promote colorectal cancer by lowering α-ketoglutarate levels and thereby promoting DNA hypermethylation, Wnt signaling and cellular de-differentiation.

To demonstrate the long-range effects of CD8⁺ T cell–secreted interferon-γ on bystander tumor cells, two studies now use mosaic models of antigen loss in tumors combined with intravital imaging. Factors that influence the length scale of diffusible signals could shape disease progression in cancer and autoimmunity.

A new suite of studies from the Pan Cancer Analysis of Whole Genomes (PCAWG) Consortium provides the most detailed resolution of cancer genomes to date, extending our knowledge of driver genes, mutational features, structural alterations and more. Kreisberg, Ideker, Mills and Meric-Bernstam discuss the foundational and translational insights gained from this project.

Evaluation of circulating tumor DNA in blood has emerged as a powerful technology for oncology research. Lillian Siu and colleagues review the potential applications of liquid biopsy, highlighting clinical-trial designs to establish its clinical utility.

Two papers by Schumacher and colleagues and Bousso and colleagues show that sensing of IFN-γ by a small number of tumor cells leads to propagation of IFN-γ sensing and response across a larger fraction of the tumor.

Two papers by Schumacher and colleagues and Bousso and colleagues show that sensing of IFN-γ by a small number of tumor cells leads to propagation of IFN-γ sensing and response across a larger fraction of the tumor.

Amgalan et al. identify BAX as a therapeutic target to prevent chemotherapy-induced cardiotoxicity without affecting the antitumor properties of doxorubicin.

Autry et al. combine genome-wide genomic, epigenetic and transcriptomic analyses in an integrated polygenomic approach to identify mechanisms of glucocorticoid resistance in acute lymphoblastic leukemia.

Tran et al. show that environmental glutamine restriction promotes Wnt signaling and intestinal tumorigenesis, whereas supplementation of the metabolite α-ketoglutarate has the reverse effect, reducing tumor growth and extending survival.

Poirier and colleagues have developed a system for in vivo genome editing of patient-derived xenografts using inducible CRISPR-Cas9 and demonstrate applications for modeling gene dependencies and drug resistance.