Trends in cancer最新文献

Genomic amplifications and hotspot mutations affecting fibroblast growth factor receptors (FGFRs) have long been recognized as oncogenic drivers across human cancers. However, recent studies have uncovered FGFR in-frame fusions and complex structural variants as an additional class of tumor driver alterations. Notably, the identification of FGFR2 exon 18 truncations and the demonstration of their potent oncogenic competence have refined our understanding of FGFR-driven tumorigenesis and have impacted clinical trial design for FGFR-targeted agents. This review explores the biological and clinical implications of FGFR rearrangements. It covers their mechanisms in driving cancer, their potential as biomarkers to predict treatment response, and the emerging challenges and opportunities for FGFR-targeted therapy. Ultimately, a deeper understanding of FGFR rearrangements is critical for advancing precision oncology and improving patient benefit.

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.

The role of lipids in cancer progression has become a fervent area of exploration. The crosstalk of tumors with adipose tissue is a complex but well-regulated orchestration of signaling pathways, lipid transporters, and enzymes. They regulate fatty acid synthesis, their deposition into lipid droplets (LDs) as triglycerides, induction of lipolysis, shuttling lipids across cells, and their systemic trafficking, modification, and catabolism. For the latter, lipid oxidation has emerged as a metabolic process of particular clinical importance. Products of lipid processing can become secondary messengers, contribute to reactive oxygen species (ROS) generation, stimulate the production of antioxidants, and, if left unchecked, activate cell death pathways including ferroptosis. This review discusses recent updates in the field that are anticipated to have therapeutic implications.

Tumors dynamically interact with the central and peripheral nervous systems, hijacking neural plasticity and reprogramming metabolism in a bidirectional manner to drive cancer progression. Neural inputs reshape the metabolism of cancer cells and their microenvironment - glycolysis, oxidative phosphorylation, and lipid metabolism - while tumors exploit neuronal nutrients and mitochondria to thrive under metabolic stress. This review explores neurocancer metabolic crosstalk through multiple mechanisms by three principal modes of interaction, highlighting how targeting these metabolic interdependencies could disrupt tumor progression. By integrating cancer metabolism and neuroscience, it offers a conceptual framework for understanding neural-tumor metabolic circuits in malignancy and identifies potential therapeutic vulnerabilities.

Classically, major histocompatibility complex class I (MHC I) molecules present tumor antigens to prime CD8⁺ T cell immunosurveillance and induce antitumor responses. Recently, Chemla et al. revealed a new immune evasion mechanism of melanoma by exporting peptide-loaded MHC I on secreted melanosomes to act as decoys that confuse and impair cytotoxic CD8⁺ T cells.

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.

Surgical resection of brain tumors is guided by radiology, anatomical relationships to critical neurological structures, and clinical metrics including patient age and neurological status. Intraoperative decision-making relies on histological assessment through smear and frozen section analysis of tissue; however, such approaches may be insufficient in the era of precision neuro-oncology. Molecular characterization now informs diagnosis, prognosis, and therapeutic response - factors that may directly influence surgical decisions. The integration of novel and rapid intraoperative diagnostic modalities holds the potential to enhance neurosurgical precision, reduce procedure-related morbidity, and maximize the overall effectiveness of modern multimodal brain tumor management.

A recent study published in Nature by Tian et al. identifies UDSP-Hep as a synthetic agonist of the innate immune receptor Alpha-protein kinase 1 (ALPK1) that induces enhanced antitumor activity compared with the canonical ALPK1 agonist ADP-Hep and Toll-like receptor or stimulator of interferon genes agonists. UDSP-Hep drives the tumor microenvironment toward a proinflammatory, antitumor state.

Tumor-associated sensory nerves are emerging regulators of cancer immunity, yet their role in systemic immunosuppression remains unclear. Zhang et al. revealed that tumors hijack an interorgan nociceptor-slit guidance ligand 2-calcitonin gene-related peptide circuit to escape immune surveillance. Disrupting this neural loop restores T-cell function and enhances immunotherapy efficacy.

MAX is the essential binding partner of MYC, necessary for MYC-dependent transcriptional activation. Depending on the context, MAX can function as a tumor suppressor or promote tumorigenesis in an MYC-driven manner. Here, we highlight the key discoveries defining the role of MAX in cancer and the current research gaps.