Trends in cancer最新文献

Renal cell carcinoma (RCC) outcomes are shaped by a complex tumor microenvironment (TME), where malignant cells represent only a minority of the tissue. Recent advances in single-cell technologies - including single-cell RNA sequencing, single-nucleus RNA sequencing, single-cell assay for transposase-accessible chromatin sequencing, single-cell T-cell receptor sequencing, and imaging mass cytometry - have uncovered the cellular, regulatory, and spatial heterogeneity of RCC. Here, we synthesize insights from these approaches to define diverse CD8⁺ T-cell subsets and exhaustion trajectories, as well as the origins, phenotypic diversity, and functional states of other immune cells including tumor-associated macrophages, dendritic cells, natural killer cells and cancer-associated fibroblasts. Together, these findings highlight the transformative potential of single-cell technologies to unravel TME complexity, identify biomarkers of therapeutic response, and guide precision immunotherapy in RCC.

Chromosomal instability (CIN) fuels phenotypic cancer heterogeneity through heritable epigenetic defects, hence driving disease initiation, progression, and resistance to therapy. Two recent studies, by Bai et al. and Salinas-Luypaert et al., demonstrate that imbalanced histone or DNA methylation actively promotes CIN by disrupting centrosome homeostasis or centromere integrity, globally linking epigenetic dysregulation to mitotic failure and genome instability.

Brain metastasis (BrM) represents the most common intracranial malignancy, arising in up to 30% of all adult cancer patients and contributing significantly to cancer-related morbidity and mortality. BrM is now recognized as a biologically distinct condition with unique mechanisms of organotropism, colonization, and therapeutic vulnerability. We highlight recent progress in omic and spatial profiling, which has revealed key drivers of brain tropism. These findings have reshaped therapeutic strategies, leading to clinical trials that specifically address central nervous system (CNS) involvement. Emerging approaches now include efforts to prevent brain relapse. Preclinical models increasingly provide sophisticated platforms to evaluate next-generation therapies. Collectively, these advances are transforming the clinical landscape, offering new hope for the prevention and management of BrM through precision medicine and integrated therapeutic strategies.

The serotonin transporter (SERT) and histone H3 serotonylation (H3Q5ser) integrate extracellular neurotransmitter signals to chromatin regulation in cancer. Here, we discuss how the SERT-H3Q5ser axis shapes tumor immunity and epigenetic plasticity, and highlight emerging strategies to therapeutically target this neuro-epigenetic interface.

CX3CL1 (fractalkine) is a unique chemokine with dual roles in cancer biology, capable of exerting both tumor-promoting and tumor-suppressive effects. Acting through its receptor CX3CR1, CX3CL1 facilitates immune evasion, angiogenesis, metastasis, and tumor cell survival and proliferation by recruiting immunosuppressive myeloid-derived suppressor cells. Conversely, it can enhance antitumor immunity by attracting cytotoxic T lymphocytes, natural killer cells, and dendritic cells into the tumor microenvironment. CX3CL1 has also been implicated in promoting immunogenic cell death-induced anticancer immune responses. However, excessive expression of CX3CL1 may paradoxically suppress immune activation, highlighting the importance of dose and context in its application. CX3CL1-based gene or mRNA therapies, particularly in combination with immune checkpoint inhibitors, show promising potential for cancer treatment.

RAS genes encode molecular switches that control cell growth and survival, and their oncogenic mutations drive many cancers. Once deemed 'undruggable', RAS is now being challenged by innovative inhibitors. Recent advances, reported by Stanland and Huggins et al. and Feng et al., include EFTX-G12V, an EGFR-directed allele-specific RNAi therapeutic, and MCB-36, a dual-state pan-KRAS degrader, exemplifying precision RAS-targeted strategies.

It is widely recognized that cancer develops through a series of changes that modify the genomes of normal cells, enabling them to acquire new malignant properties. Epigenetic disruptions, which do not directly change the genetic sequence but rather influence how the genome is interpreted, have garnered significant attention as contributors to malignant transformation and progression. With the advent of new technologies to profile both the genome and epigenome of cancer cells simultaneously, the interplay between structural variation (SV) and epigenetic changes in malignancy is now an expanding field. In this review, we describe the key technological advances and highlight recent research exploring the relationship between SV and the epigenome in cancer.

Viral mimicry is a cellular state in which the reactivation of silenced transposable elements (TEs) leads to the accumulation of immunogenic nucleic acids, triggering innate immune pathways that resemble responses mounted against viral pathogens. Although they were first characterized in the context of epigenetic therapies, growing evidence indicates that other cancer treatment modalities - including radiotherapy, chemotherapies, and targeted therapies - can also induce TE reactivation and viral mimicry responses in cancer cells. This review synthesizes the current knowledge on treatment-induced TE-mediated immune responses in cancer, highlighting therapeutic strategies, shared and distinct molecular mechanisms, and their broader implications for tumor-immune interactions and treatment outcomes.

Circulating tumor cell (CTC) clusters have emerged as key mediators of cancer spread. Among these, heterotypic CTC clusters exemplify how cooperative interactions between different cell types may enhance metastasis efficiency. Recent studies by Scholten et al. and Schuster et al. uncover additional immune cell partners, including T cells and monocytes, involved in shaping CTC biology.

The tumor microenvironment (TME) imposes profound metabolic and functional constraints on immune cells, with mitochondrial dysfunction emerging as a pivotal driver of immunosuppression. While mitochondrial metabolism is well recognized for its role in energy production and cellular homeostasis, its dynamic regulation of immune cell activation, differentiation, and exhaustion within the TME remains underexplored. In this review we summarize insights into how TME stressors such as hypoxia, nutrient competition, and metabolic byproducts subvert mitochondrial dynamics, redox balance, and mitochondrial DNA (mtDNA) signaling in T cells, natural killer (NK) cells, and macrophages, thereby directly impairing their antitumor efficacy. We emphasize that the restoration of mitochondrial fitness in immune cells, achieved by targeting metabolites in the TME and mitochondrial quality control, represents a pivotal axis for adoptive cell therapies (ACTs) and TME reprogramming.