Trends in cancer最新文献

Short-chain fatty acids (SCFAs), derived from the diet and the microbiota, serve as crucial links between the diet, gut microbiota, metabolism, immunity, and cancer. They function as energy sources through β-oxidation and regulate macromolecular synthesis, G protein-coupled receptor (GPCR) and histone deacetylase (HDAC) activities, protein modifications, signaling pathways, and gene expression in cells within the tumor microenvironment, particularly in tumor and immune cells. The critical role of SCFAs in maintaining normal homeostasis and influencing tumor progression highlights the potential of targeting SCFA-mediated cellular processes for cancer prevention and treatment.

The mechanisms underlying the potential 'anticancer' effects of exercise remain poorly understood. Luo et al. recently identified an exercise-induced, muscle-derived extracellular vesicle (EV)-associated miR, miR-29a-3p, as a key player in the potential benefits of exercise against nonsmall-cell lung carcinoma (NSCLC), including extracellular matrix (ECM) inhibition and improved antitumoral immune responses.

Genetic immune escape (GIE) alterations pose a significant challenge in cancer by enabling tumors to evade immune detection. These alterations, which can vary significantly across cancer types, may often arise early in clonal evolution and contribute to malignant transformation. As tumors evolve, GIE alterations are positively selected, allowing immune-resistant clones to proliferate. In addition to genetic changes, the tumor microenvironment (TME) and non-genetic factors such as inflammation, smoking, and environmental exposures play crucial roles in promoting immune evasion. Understanding the timing and mechanisms of GIE, alongside microenvironmental influences, is crucial for improving early detection and developing more effective therapeutic interventions. This review highlights the implications of GIE in cancer development and immunotherapy resistance, and emphasizes the need for integrative approaches.

Autophagy has a dual role in tumor progression and therapy, influenced by specific receptors and cargo selection. Recent research published in Cell by Herhaus et al. identifies immunity-related GTPase Q (IRGQ) as a novel autophagy receptor that facilitates immune evasion in hepatocellular carcinoma (HCC) by degrading histocompatibility complex class I (MHC-I) molecules, highlighting a potential target to enhance immunotherapy.

Neoadjuvant immune checkpoint inhibition (ICI) is a new approach to treat patients with colorectal cancer (CRC). The effects of combined neoadjuvant ICI in locally advanced, DNA mismatch repair (dMMR)-deficient/microsatellite instable (MSI) CRC were recently reported by de Gooyer et al. from the NICHE-3 trial. Further studies will determine whether these impressive pathological responses lead to long-term clinical benefit.

The enhancer of zeste inhibitory protein (EZHIP) is typically expressed during germ cell development and has been classified as a cancer-testis antigen (CTA) in various cancers. In 2020, 4% of diffuse midline gliomas (DMGs) were shown to aberrantly express EZHIP, mirroring the DMG hallmark histone H3 K27M (H3K27M) oncohistone mutation. Similar to H3K27M, EZHIP is a negative regulator of polycomb repressive complex 2 (PRC2), leading to global epigenomic remodeling. In this opinion, we explore the similarities and disparities between H3K27M- and EZHIP-DMGs with a focus on their shared functional hallmark of PRC2 inhibition, their genetic and epigenomic landscapes, plausible differences in the cell of origin, and therapeutic avenues. Upcoming research on EZHIP will help better understand its role in gliomagenesis and DMG therapy.

Tumor-associated epilepsy is the most common presenting symptom in patients diagnosed with diffuse gliomas. Recent evidence illustrates the requirement of synaptic activity to drive glioma proliferation and invasion. Class 1, 2, and 3 evidence is limited regarding the use of antiepileptic drugs (AEDs) as antitumor therapy in combination with chemotherapy. Furthermore, no central mechanism has emerged as the most targetable. The optimal timing of AED regimen remains unknown. Targeting aberrant neuronal activity is a promising avenue for glioma treatment. Clinical biomarkers may aid in identifying patients most likely to benefit from AEDs. Quality evidence is needed to guide treatment decisions.

The tumor microenvironment (TME) represents a dynamic network of cancer cells, stromal cells, immune mediators, and extracellular matrix components, crucial for cancer progression. Stress conditions such as oncogene activation, nutrient deprivation, and hypoxia disrupt the endoplasmic reticulum (ER), activating the unfolded protein response (UPR), the main adaptive mechanism to restore ER function. The UPR regulates cancer progression by engaging cell-autonomous and cell-non-autonomous mechanisms, reprogramming the stroma and promoting immune evasion, angiogenesis, and invasion. This review explores the role of UPR beyond cancer cells, focusing on how ER stress signaling reshapes the TME, supporting tumor growth. The therapeutic potential of targeting the UPR is also discussed.

Growth factors signal through engagement and activation of their respective cell surface receptors to choreograph an array of cellular functions, including proliferation, growth, repair, migration, differentiation, and survival. Because of their vital role in determining cell fate and maintaining homeostasis, dysregulation of growth factor pathways leads to the development and/or progression of disease, particularly in the context of cancer. Exciting advances in protein engineering technologies have enabled innovative strategies to redesign naturally occurring growth factor ligands and receptors as targeted therapeutics. We review growth factor protein engineering efforts, including affinity modulation, molecular fusion, the design of decoy receptors, dual specificity constructs, and vaccines. Collectively, these approaches are catapulting next-generation drugs to treat cancer and a host of other conditions.

Brain tumors in children and adults differ greatly in patient outcomes and responses to radiotherapy and chemotherapy. Moreover, the prevalence of recurrent mutations in histones and chromatin regulatory proteins in pediatric and young adult gliomas suggests that the chromatin landscape is rewired to support oncogenic programs. These early somatic mutations dysregulate widespread genomic loci by altering the distribution of histone post-translational modifications (PTMs) and, in consequence, causing changes in chromatin accessibility and in the histone code, leading to gene transcriptional changes. We review how distinct chromatin imbalances in glioma subtypes impact on oncogenic features such as cellular fate, proliferation, immune landscape, and radio resistance. Understanding these mechanisms of epigenetic dysregulation carries substantial implications for advancing targeted epigenetic therapies.