Trends in cancer最新文献

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.

Tumor-infiltrating lymphocyte (TIL) therapy has demonstrated efficacy in refractory melanoma and durable responses in lung cancer. Glioblastoma presents distinct challenges for immunotherapy, including profound tumor heterogeneity, low T cell infiltration, and an immunosuppressive microenvironment, but these same features highlight the unique rationale for TILs. Unlike monoclonal engineered approaches, TILs retain natural polyclonality, enabling recognition of a diverse set of tumor-associated antigens and potential adaptation to the evolving antigenic landscape. Preliminary studies have already shown that tumor-reactive TILs can be successfully isolated and expanded from glioblastoma specimens, providing feasibility for clinical translation. This review discusses the current landscape of TIL therapy in glioblastoma, highlights recent advancements, and discusses future directions and clinical translation to position TIL therapy as a promising and adaptable cellular immunotherapy for one of the most treatment-resistant human cancers.

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.

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.

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.

While the initial transformation of cancer cells is driven by genetic alterations, tumor cell behaviors and functional states are dynamically regulated by cell-intrinsic factors including proteins, metabolites and lipids, and extrinsic microenvironmental factors. Emerging multi-omics technologies highlighted that cancer cells exhibit distinct lipidome compositions and employ specific lipid metabolic circuits for chemical conversions - collectively defined as 'lipotypes'. We review the interplay between cancer lipotypes and cellular states, focusing on interpreting how being at different positions along the spectra of representative lipid metabolic axes influences cancerous traits. We aim to instill a system biology perspective to integrate 'lipotypes' into the established 'genotype-phenotype' framework in cancer.

Whole-genome doubling (WGD) has recently emerged as one of the most common genomic alterations in cancer and is associated with genomic instability, drug resistance, and metastasis. However, WGD also generates unique vulnerabilities that create a therapeutic window between cancer cells and healthy cells. Over the past few years, there has been a rapid growth in our understanding of WGD at a molecular level. In this review, we discuss the causes and immediate cellular effects of, and therapeutic considerations for, WGD in cancer.

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.

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.