Trends in cancer最新文献

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.

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.

Fairness in artificial intelligence (AI) is often assessed with flawed metrics, particularly in oncology where patient diversity and structural inequities shape outcomes. Ground truth labels, predictions, and demographic attributes all carry biases that distort fairness evaluations. We argue for rethinking fairness frameworks to better capture equity in cancer care.

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.