In this issue of Molecular Cell, Toda et al. (2020) show that postprandial elevation of LPS and insulin induce the production of IL-10 by adipose tissue macrophages. Hepatic gluconeogenesis is then inhibited synergistically by insulin and IL-10 to facilitate glucose clearance.

Kong et al. (2020) present the low-resolution structure of the ATPɣS-bound human condensin I and II complexes and demonstrate that human condensins can extrude DNA loops in a symmetric and asymmetric fashion and compact nucleosome-bound DNA.

Cell surface MHC-I can present tumor antigens to CD8+ T cells. In pancreatic cancer, selective autophagy instead reroutes MHC-I to lysosomes, using the ubiquitin-binding receptor NBR1, precluding T cell recognition. Accordingly, immune clearance of tumors can be facilitated by blocking autophagy.

The CRISPR-Cas system offers a programmable platform for eukaryotic genome and epigenome editing. The ability to perform targeted genetic and epigenetic perturbations enables researchers to perform a variety of tasks, ranging from investigating questions in basic biology to potentially developing novel therapeutics for the treatment of disease. While CRISPR systems have been engineered to target DNA

We recently used CRISPRi/a-based chemical-genetic screens and cell biological, biochemical, and structural assays to determine that rigosertib, an anti-cancer agent in phase III clinical trials, kills cancer cells by destabilizing microtubules. Reddy and co-workers (Baker et al., 2020, this issue of Molecular Cell) suggest that a contaminating degradation product in commercial formulations of rigosertib

Combination therapy remains the cornerstone for cancer management, and understanding how to rationally partner drugs is imperative. In this issue of Molecular Cell, Shu et al. (2020) provide a tour de force multi-omic approach to identify synergistic pathways that increase the efficacy of BET bromodomain inhibitors in triple-negative breast cancer.

In this issue of Molecular Cell, Wu et al. (2020) describe studies that establish oncogenic versus tumor-suppressive functions of two BRD4 isoforms in the regulation of gene expression and breast cancer development.

In this month’s issue of Cancer Cell, Su et al. (2020) describe two small-molecule inhibitors of the RNA demethylase FTO that demonstrate significant anti-tumor effects in various models of acute myeloid leukemia.

In a breakthrough study in a recent issue of Cell, Michealraj et al. (2020) demonstrate that posterior fossa A ependymoma, a lethal pediatric brain tumor with a silent genome, is dependent upon metabolic changes associated with hypoxia that drive the tumor’s characteristic epigenetic dysregulation.

We are witnessing several revolutionary technological advances in cancer. These innovations have not only contributed to a growing understanding of the tumor and its microenvironment but also uncovered an increasing array of new therapeutic targets. For most advanced cancers, therapy resistance limits the benefit of single-agent therapies. Therefore, some 5,000 clinical trials are ongoing globally

The growing field of immune metabolism has revealed promising indications for metabolic targets to modulate anti-cancer immunity. Combination therapies involving metabolic inhibitors with immune checkpoint blockade (ICB), chemotherapy, radiation, and/or diet now offer new approaches for cancer therapy. However, it remains uncertain how to best utilize these strategies in the context of the complex

Malignant cells remodel their metabolism to meet the demands of uncontrolled cell proliferation. These demands lead to differential requirements in energy, biosynthetic precursors, and signaling intermediates. Both genetic programs arising from oncogenic events and transcriptional programs and epigenomic events are important in providing the necessary metabolic network activity. Accumulating evidence

Cell death, or, more specifically, cell suicide, is a process of fundamental importance to human health. Throughout our lives, over a million cells are produced every second. When organismal growth has stopped, to balance cell division, a similar number of cells must be removed. This is achieved by activation of molecular mechanisms that have evolved so that cells can destroy themselves. The first

Ca2+ ions are key second messengers in both excitable and non-excitable cells. Owing to the rather pleiotropic nature of Ca2+ transporters and other Ca2+-binding proteins, however, Ca2+ signaling has attracted limited attention as a potential target of anticancer therapy. Here, we discuss cancer-associated alterations of Ca2+ fluxes at specific organelles as we identify novel candidates for the development

Anti-cancer drugs targeting the DNA damage response (DDR) exploit genetic or functional defects in this pathway through synthetic lethal mechanisms. For example, defects in homologous recombination (HR) repair arise in cancer cells through inherited or acquired mutations in BRCA1, BRCA2, or other genes in the Fanconi anemia/BRCA pathway, and these tumors have been shown to be particularly sensitive

Transcription is epigenetically regulated by the orchestrated function of chromatin-binding proteins that tightly control the expression of master transcription factors, effectors, and supportive housekeeping genes required for establishing and propagating the normal and malignant cell state. Rapid advances in chemical biology and functional genomics have facilitated exploration of targeting epigenetic