Trends in cancer最新文献

Multi-omics integration is reshaping cancer research by combining histopathology, transcriptomics, and proteomics with spatial and temporal context. Schweizer et al. revealed compartment-specific biology, RNA-protein decoupling, and emergent molecular patterns underpinning malignant transformation in low-grade serous carcinoma, highlighting the potential of integrated multi-omics to uncover novel mechanisms and guide precision oncology.

Cancer cells undergo metabolic reprogramming to sustain their energy demands, and favor glycolysis despite the presence of functional mitochondria. This metabolic shift leads to the rapid production of lactate and protons. If not managed, this accumulation of acidic byproducts would lower the intracellular pH (pH_i). To counteract this, cancer cells employ diverse mechanisms to extrude excess protons through membrane transporters, and also sequester them within acidic organelles. Consequently, an alkaline pH_i provides cancer cells with a survival advantage by promoting their proliferation, migration, and resistance to cell death. Given the role of organellar acidification in sustaining this altered pH balance, targeting this process represents a potential therapeutic vulnerability in cancer. We explore the mechanisms by which cancer cells maintain pH homeostasis, with a particular focus on organellar pH and its impact on tumor progression. In addition, we assess inhibitors of the key transporters involved in organellar acidification and discuss their therapeutic potential in cancer.

Stem-like CD8⁺ T cells - characterized by high-level expression of the transcription factor TCF-1, and known as progenitor exhausted T (T_pex) cells - have emerged as crucial mediators of durable antitumor immunity. These cells demonstrate unique self-renewal capacity, multipotency, and enhanced responsiveness to immune checkpoint blockade therapy. This review synthesizes current understanding of T_pex cell biology, including their defining characteristics, tissue distribution, and functional importance in antitumor immunity. We focus particularly on innovative approaches to preserve and enhance T cell stemness through combination therapies, cytokine signal modulation, epigenetic regulation, tumor microenvironment modification, and microbiota-based interventions. The development of these next-generation immunotherapies targeting T cell stemness represents a transformative frontier in oncology, holding significant promise for improving therapeutic outcomes in cancer patients.

RNA-binding proteins (RBPs) govern RNA-based post-transcriptional processes that generate the abundance and diversity of the proteome. RBPs have recently emerged as crucial cancer regulators that can influence multiple cancer hallmarks. However, many RBPs display remarkable variations across different tumor types and can exert both tumor-promoting and tumor-suppressive effects. These opposing roles are often attributed to context-dependency, but there is a distinct lack of clarity regarding what aspects of cellular context define the differences in the roles of RBPs. Given the recent development of RBP-targeted interventions, resolving this significant gap in the field could improve the selectivity and specificity of RBP biomarkers and therapies in cancer. This review analyzes recent findings and explores the mechanisms by which the functional plasticity of RBPs in tumorigenesis may arise.

Although interest in antigen-presenting cancer-associated fibroblasts (apCAFs) is increasing, their therapeutic potential remains poorly understood. In a recent study, Chen et al. reveal two osteopontin-expressing apCAF populations present across malignancies and distinct in origin and location: mesothelial-like (M-)apCAFs, which are found near cancer cells, and fibrocyte-like (F-)apCAFs, which associate with lymphocyte-enriched niches.

Stem cell-like blasts have been associated with hierarchical tumor-initiating potential and poor outcomes in myeloid leukemias. Previous studies using primary samples of acute lymphoblastic leukemia (ALL) have identified blasts that immunophenotypically and transcriptomically resemble hematopoietic stem and progenitor cells (HSPCs), but failed to consistently demonstrate hierarchical tumor-initiating potential in xenograft models. Recent multi-omic profiling of lymphoblastic and mixed-phenotype leukemias has improved our understanding of the phenotypes of HSPC-like blasts and their association with treatment failure, relapse, and lineage switch during therapy. In this review, we highlight the opportunities and challenges of using HSPC-like blasts to risk-stratify patients with ALL and direct patients with relapsed/refractory disease toward targeted therapies.

Cuproptosis, a recently discovered form of regulated cell death triggered by copper overload, is distinguished by the aggregation of lipoylated mitochondrial proteins and destabilization of iron-sulfur cluster proteins. Given the altered copper metabolism and metabolic dependencies of cancer cells, cuproptosis might represent a unique vulnerability with therapeutic potential. In this review we summarize current knowledge of copper homeostasis, the molecular mechanisms of cuproptosis and its roles in cancer biology. We highlight therapeutic strategies that harness cuproptosis, including copper ionophores, nanomedicine, and rational combination therapies, and discuss challenges such as systemic toxicity, resistance mechanisms, and biomarker development. Finally, we outline key questions and future directions for translating cuproptosis into the clinic.

Traditionally neglected and frequently excluded from large-scale genomic studies, the Y chromosome is now emerging as a potential Achilles' heel of cancers in men. Recent evidence has suggested that loss of this chromosome - a phenomenon known as loss of Y chromosome (LOY) - is not a silent event, but rather an active driver that promotes tumor progression through loss of tumor suppressor genes, increasing tumor growth and enabling immune evasion. Importantly, LOY creates loss of heterozygosity of paralogous genes on the X chromosome, a vulnerability that can potentially be therapeutically exploited. The exact mechanisms of LOY in cancer, and the utility of LOY as a biomarker and therapeutic target, are open questions for the emerging field of Y chromosome-focused cancer research.

Small-cell lung cancer (SCLC) is an aggressive neuroendocrine (NE) tumor and a leading cause of cancer-related morbidity. The introduction of immune checkpoint inhibitors (ICIs) transformed the treatment of many other cancers but has so far failed to benefit all but a minority of SCLC patients who gain a modest increase in overall survival. Although SCLC is often considered to be 'immune-cold', there is no consensus mechanistic view on why most patients fail to respond to ICI therapy. We address this important question by reviewing recent genomic profiling studies that reveal a complex immune landscape. Each molecular subtype is associated with a unique pattern of immune infiltration and a program of cellular plasticity that involves loss of NE traits. This immunobiology presents a rapidly evolving case study in mechanisms of ICI response and resistance. We discuss recent developments, present new hypotheses, and explore future directions for the field.

Cytotoxic chemotherapy (CC) has long been the cornerstone of treatment in oncology, but primary resistance, the emergence of secondary resistance, and toxicity remain significant challenges. We explore how precision oncology aims to replace conventional chemotherapy through its enhanced antitumoral activity and reduced toxicity. We highlight significant progress in this area and emphasize recent clinical trials where targeted therapies and immunotherapy have yielded superior outcomes. Despite significant advances in cancer understanding and molecular profiling, in the coming years CC will likely remain a standard treatment for diseases that are not accessible to precision oncology or immunotherapy, as a rescue treatment for many cancers, or in combinations with new agents.