Search

The formation of C-C bonds in fatty acid and polyketide biosynthesis depends on β-ketoacyl-acyl carrier protein (ACP) synthases (KSs). Here, the authors present structures of E.coli KSs bound to substrate mimetic bearing ACPs, providing insights into the catalytic mechanism underlying C-C bond forming reactions.

In mammals there are two Musashi proteins, MSI1 and MSI2, orthologues of the Drosophila protein, with roles in asymmetric stem cell division and cell fate determination. Here the authors report new functions for MSI2 in colorectal cancer using in vitro loss of function and in vivoectopic overexpression.

This study uses a combination of in silico and experimental techniques to ascribe target genes to 170 risk loci for colorectal cancer.

Shi et al. present a hybrid dependency map based on machine-learning analysis of gene essentiality data from the DEPMAP database, translated to data from TCGA. This application can be used to visualize other gene essentiality data.

The immunocytokine NHS-IL12 is targeted to necrotic tumour areas to prompt an immune response. Authors show here in mouse colon and breast models that the combination of histone deacetylase inhibitor, Entinostat, and NHS-IL12 generates a tumour microenvironment that favours tumour resolution.

Nusrat Epsi et al. present pathCHEMO, a computational framework for uncovering transcriptomic and epigenomic pathways of chemoresistance in cancer that has the potential to improve clinical decision-making. They apply pathCHEMO to lung adenocarcinoma data from public databases, and identify seven molecular pathways implicated in carboplatin-paclitaxel resistance.

Rare cancer mutations are often missed using recurrence-based statistical approaches, but are usually accompanied by changes in expression. Here the authors leverage this information to uncover several elusive candidate cancer-associated genes using topological data analysis.

Jacks and colleagues demonstrate the effects of neoantigen expression level on T-cell priming and immune surveillance during tumor development and progression and explore implications for immunotherapies, using in vivo models of colorectal cancer.

Data provided by Amazonian peoples are used to estimate the value of wild animals as a source of food, including its spatial distribution and nutritional value, providing information that will be key for improved management of forest ecosystems in the region.

In cells with microsatellite instability, expanded TA-dinucleotide repeats form cruciform structures that stall replication forks and cause chromosome shattering in the absence of the WRN helicase.

Colorectal cancer can lead to the development of peritoneal metastases, which are associated with worse disease outcome. Here, the authors characterize peritoneal metastases from 52 patients using RNA-seq and mutational sequencing and show a distinct molecular subtype.

The presence of classical type 1 dendritic cells (cDC1) positively influences prognosis in cancer, but their intricate networking with the various T cell types found in the tumour microenvironment is not fully appreciated. Here the authors show that cDC1 encounter with CD4⁺ helper T-cells transforms their gene expression signature, and these “helped” dendritic cells enable the function of anti-tumour cytotoxic T-cells.

Interactions between plexin B2 on hepatocytes and sempahorins on disseminated tumour cells regulate metastatic seeding in the liver.

Multi-omics can be used to characterise tumour and immune cell populations. Here the authors use multi-omics to characterise CLL blood and tissue samples and use prediction models for CLL TCR specificity and implicate interactions between galectin-9 and TIM3 as involved in CLL immune escape and propose galectin-9 as a possible immunotherapy target.

Promoter capture Hi-C in colorectal cancer cells integrated with cancer genome and expression data identifies a noncoding, cis-regulatory element that is recurrently mutated in cancer, affecting ETV1 expression, cell viability and patient survival.

It has been previously shown that combining immune checkpoint inhibitors with TGFβ blockade potentiates anti-tumor immune responses. Here the authors show that, in an immune excluded preclinical tumor model, combining therapeutic anti-PD-L1 with anti-TGFβ treatment promotes expansion and differentiation of stem-cell like CD8 + T cells.

Normal tissue adjacent to the tumour (NAT) is often used as a control in cancer studies. Here, the authors analyse across cancer types the transcriptomes of healthy, NAT, and tumour tissues, and find that NAT presents a unique state, potentially due to inflammatory response of the NAT to the tumour tissue.

Cancer cells that have undergone whole-genome doubling are more reliant than their near-diploid counterparts on DNA-replication factors, the spindle-assembly checkpoint and a mitotic kinesin protein, KIF18A.

RAC1 is a downstream target of the Wnt signaling that promotes intestinal stem cell expansion and tumorigenesis. Here, the authors identify the specific splice variant RAC1B as an important mediator of colorectal tumourigenesis and a potential target for enhancing the efficacy of EGFR inhibitor treatment.

The importance of the tumour microenvironment has now been realised, however the presence of non-tumour cells in cancer samples can complicate genomic analyses. Here, the authors estimate tumour purity in 10,000 samples from the TCGA dataset and can detect a signature of T cell activation.

Temozolomide therapy seems to lead to mismatch repair deficiency and hypermutation in gliomas, but not to an increase in response to immunotherapy.

A method, RARE-seq, for sensitive detection of cell-free RNAs in blood is demonstrated to have diverse clinical applications including diagnosing and characterizing human cancers, and tracking response to RNA therapeutics.

Inherent or acquired resistance to treatment of glioblastoma (GBM) is nearly universal. Here, the authors introduce a platform to identify synergistic drug combinations for patient-specific treatment of GBM based on gene expression signatures and small molecule perturbation-response profiles.

Kinases regulate cellular processes, making their study essential for understanding cellular function and disease. Here, the authors evaluate methods to infer kinase activity from phosphoproteomics data and provide a toolkit to evaluate future methods.

A summary of CAR T-cell engineering approaches, including functional screening methods, gene editing and delivery advances, and optimization of metabolic fitness.

Whole-genome DNA methylation profiling and analysis of normal tissues from both human and mouse reveal that hypomethylation within partially methylated, late-replicating domains depends on sequence context, starts early in development, accumulates with cell divisions and progresses with organismal aging.

Circulating cell-free DNA (cfDNA) assays for monitoring individuals with cancer typically use tumor-specific mutations that may not be detected in many patients. Here, the authors develop a tumor-independent and mutation-independent approach (DELFI-TF) to estimate tumor burden in cfDNA for treatment response monitoring and clinical outcome prediction.

Andrea Califano, Mariano Alvarez and colleagues present an approach, VIPER, for inferring protein activity in single cancer samples based on expression of a protein's downstream targets. The authors use VIPER to predict aberrant protein activity independent of mutational status and validate drug sensitivity predictions using in vitro assays.

A pan-cancer epigenetic and transcriptomic atlas identifies epigenetic drivers associated with cancer transitions.

Polyamine metabolism is frequently dysregulated in cancers. Here, the authors show that a polyamine biosynthetic enzyme, spermine synthase, is overexpressed in colorectal cancers and cooperates with MYC to prevent cancer cell apoptosis by repression of proapoptotic protein, Bim.

Song et al. developed a computational tool to profile binding pairs between tumor-derived antigens and antibodies from high-throughput B cell receptor sequencing data, predicting response to immune-checkpoint inhibitor therapy and risk of adverse events.

In lung cancer, relatively few germline mutations are known to impact risk. Here the authors looked at rare variants in 39,146 individuals and find novel germline mutations associated with risk, as well as implicating ATM and a new candidate gene for lung cancer risk.

Multiple cellular pathways are altered in cancer and identifying them is relevant for prognosis and therapy. Here, the authors develop Benchmark and Pathway Ensemble Tool (PET), two computational approaches to optimise pathway discovery in cancer and predict related biomarkers and therapeutic avenues.

This study examines karyotypic selection and evolution in vitro using immortalized mammary and kidney epithelial cell lines, observing aneuploidy patterns specific to each origin tissue that are correlated with frequencies in patient tumors and independent of drivers such as TP53 mutation.

Antibody diversification relies on the intentional mutagenesis of immunoglobulin genes for adaptive immune responses. Here, the authors identified a CTLH E3 ubiquitin ligase complex that co-opts FAM72A to recruit and degrade the UNG2 base excision repair factor to permit mutagenesis.

B7-H3 is expressed at high levels in several cancer types and can suppress antitumor immune responses. Here the authors show that B7-H3 expression is dependent on mTORC1 activity and that inhibition of B7-H3 promotes antitumor immunity mediated by cytolytic CD4 + T cells in tumor models with mTORC1 hyperactivity.