Trends in cancer最新文献

The traditional view of cancer emphasizes a genes-first process. Novel cancer traits arise by genetic mutations that spread to drive phenotypic change. However, recent data support a phenotypes-first process in which nonheritable cellular variability creates novel traits that later become heritably stabilized by genetic and epigenetic changes. Single-cell measurements reinforce the idea that phenotypes lead genotypes, showing how cancer evolution follows normal developmental plasticity and creates novel traits by recombining parts of different cellular developmental programs. In parallel, studies in evolutionary biology also support a phenotypes-first process driven by developmental plasticity and developmental recombination. These advances in cancer research and evolutionary biology mutually reinforce a revolution in our understanding of how cells and organisms evolve novel traits in response to environmental challenges.

Bispecific antibodies (bsAbs) are engineered molecules designed to target two different epitopes or antigens. The mechanism of action is determined by the bsAb molecular targets and structure (or format), which can be manipulated to create variable and novel functionalities, including linking immune cells with tumor cells, or dual signaling pathway blockade. Several bsAbs have already changed the treatment landscape of hematological malignancies and select solid cancers. However, the mechanisms of resistance to these agents are understudied and the management of toxicities remains challenging. Herein, we review the principles in bsAb engineering, current understanding of mechanisms of action and resistance, data for clinical application, and provide a perspective on ongoing challenges and future developments in this field.

Advances in cancer immunotherapy have transformed cancer care and realized unprecedented responses in many patients. The growing arsenal of novel therapeutics - including immune checkpoint inhibition (ICI), adoptive T cell therapies (ACTs), and cancer vaccines - reflects the success of cancer immunotherapy. The therapeutic benefits of these treatment modalities are generally attributed to the enhanced quantity and quality of antitumor CD8⁺ T cell responses. Nevertheless, CD4⁺ T cells are now recognized to play key roles in both the priming and effector phases of the antitumor immune response. In addition to providing T cell help through co-stimulation and cytokine production, CD4⁺ T cells can also possess cytotoxicity either directly on MHC class II-expressing tumor cells or to other cells within the tumor microenvironment (TME). The presence of specific populations of CD4⁺ T cells, and their intrinsic plasticity, within the TME can represent an important determinant of clinical response to immune checkpoint inhibitors, vaccines, and chimeric antigen receptor (CAR) T cell therapies. Understanding how the antitumor functions of specific CD4⁺ T cell types are induced while limiting their protumorigenic attributes will enable more successful immunotherapies.

Cancer researchers tend to be well-versed in communicating research and research results to scientific audiences. To maintain momentum and progress against cancer, they must acquire and nurture skills allowing for better engagement with the lay public.

Growing evidence highlights the importance of tumor endothelial cells (TECs) in the tumor microenvironment (TME) for promoting tumor growth and evading immune responses. Immunomodulatory endothelial cells (IMECs) represent a distinct plastic phenotype of ECs that exerts the ability to modulate immunity in health and disease. This review discusses our current understanding of IMECs in cancer biology, scrutinizing insights from single-cell reports to compare their characteristics and function dynamics across diverse tumor types, conditions, and species. We investigate possible implications of exploiting IMECs in the context of cancer treatment, particularly examining their influence on the efficacy of existing therapies and the potential to leverage them as targets in optimizing immunotherapeutic strategies.

Emerging evidence indicates that metabolism not only is a source of energy and biomaterials for cell division but also acts as a driver of cancer cell plasticity and treatment resistance. This is because metabolic changes lead to remodeling of chromatin and reprogramming of gene expression patterns, furthering tumor cell phenotypic transitions. Therefore, the crosstalk between metabolism and epigenetics seems to hold immense potential for the discovery of novel therapeutic targets for various aggressive tumors. Here, we highlight recent discoveries supporting the concept that the cooperation between metabolism and epigenetics enables cancer to overcome mounting treatment-induced pressures. We discuss how specific metabolites contribute to cancer cell resilience and provide perspective on how simultaneously targeting these key forces could produce synergistic therapeutic effects to improve treatment outcomes.

Recent advances in artificial intelligence (AI) have revolutionized computational pathology (CPath), particularly through deep learning (DL) and neural networks (NNs). In a recent study, Vorontsov et al. introduced Virchow, a new foundation model (FM) for CPath, which has shown promising results in cancer detection and biomarker prediction.

‘Bad bacteria’ could alter the toxicokinetics of environmental pollutants, thereby exacerbating chemically induced tumorigenesis. Recently, Roje et al. reported that specific gut microbiota can metabolize nitrosamine compounds to a toxic oxidation product, aggravating bladder cancer development and progression. These findings have important implications for tumor intervention through the gut microbiota.