Trends in cancer最新文献

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.

The urea cycle (UC) is a vital metabolic pathway that is responsible for the disposal of nitrogen and the production of metabolites necessary for biosynthesis. UC dysregulation is common in various cancers and impacts on cellular metabolism and the tumor microenvironment (TME). In this review we explore alterations in the expression of UC genes and metabolites in tumors, focusing on their roles in tumor progression, the TME, and cancer therapies. We discuss the effects of the UC on immune responses involving T cells and immunosuppressive cells, as well as on stromal cells and angiogenesis. We highlight the impact of arginine and polyamine metabolism in the TME. Although therapeutic strategies targeting the UC show promise, including arginine deprivation therapy (ADT), they face challenges such as drug resistance and toxicity. It will be essential to elucidate the specific functions of UC enzymes in tumorigenesis to devise more effective, personalized tumor therapies. Future studies should focus on combination therapies and personalized medicine to improve efficacy and patient prognosis.

IL17-secreting γδ T cells promote immunosuppression, metastatic dissemination, and resistance to treatment in various oncological settings. Recent findings from Deng et al suggest that DNA-containing extracellular vesicles released from irradiated lung cancer cells favor radioresistance by orchestrating the recruitment of IL17-secreting γδ T cells via a CCL20-dependent mechanism involving STING signaling in tumor-associated macrophages.

Ribonuclease-targeting chimeras (RIBOTACs) are innovative RNA-targeting molecules that combine small-molecule RNA binders with endogenous RNase L-recruiting moieties, enabling catalytic degradation of previously considered 'undruggable' transcripts. The unique mechanism of RIBOTACs allows them to circumvent limitations of existing RNA-targeted therapeutics, expanding their therapeutic potential in oncology.

Human papillomavirus (HPV) integration is known to cause host genome instability and subsequent structural variants. Recently, Khan and colleagues thoroughly characterized a recurrent FGFR3-TACC3 fusion caused by HPV integration in oropharyngeal squamous cell carcinoma (OPSCC) identifying synergistic interplay with HPV E6/E7 required for transformation. These findings reveal another mechanism in which virus integration can ignite tumorigenesis and a promising avenue for future investigation.

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.

Colorectal cancer (CRC) remains one of the most prevalent cancers, with treatment largely dependent on surgery and chemotherapy, underscoring the need for novel or adjunct therapies. Cancer cells reprogram their lipid metabolism to support proliferation, invasiveness, and chemoresistance, making it a promising therapeutic target. Although several inhibitors of lipogenesis, lipases, lipid uptake, and lipid storage are under investigation in CRC, none have yet shown sufficient efficacy. Importantly, the tumor microenvironment (TME) and the microbiome influence CRC lipid metabolism by supplying compensatory lipids and engaging in crosstalk that affects the efficacy of lipid-targeting therapies. This review describes the role of lipids in CRC and explores how the TME and the gut/tumor microbiome may contribute to current challenges in the development of effective lipid-targeting therapies.