Trends in cancer最新文献

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.

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.

Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous group of aggressive lymphomas driven by distinct biological pathways. Although historically divided into two major subtypes on the basis of putative cell of origin, detailed genomic analyses have revealed additional classifications with prognostic implications. Additionally, the lymphoma microenvironment adds a layer of complexity distinct from genetic subclassifications and influences disease trajectory and response to therapies. Herein, we review the emerging roles of immune-based therapies to address this complex interplay between intrinsic genetic drivers and the surrounding tumor microenvironment in DLBCL.

The dreadful liaison between platelets and tumor cells was discovered half a century ago. Since then, a plethora of studies have characterized the contribution of platelets to primary tumor development, survival of circulating tumor cells in the bloodstream, and metastatic seeding and outgrowth. Yet, although these provided a deep understanding of how platelets shape cancer progression, the field suffers from a lack of additional knowledge required to design efficient therapeutic strategies. Here, we aim to summarize recent discoveries that identify new ways in which platelets shape metastasis beyond their initial intravascular role. We further discuss platelet-borne molecular targets that could represent new avenues for therapeutically targeting platelets' contribution to metastasis.

Myeloid cell leukemia 1 (MCL-1), an antiapoptotic protein, belongs to the BCL-2 protein family and is an extensively studied anticancer target. MCL-1 inhibitors have been in development for decades but fall short on efficacy, toxicity, and side-effects. Recently, Brinkmann et al. shed light on the apoptosis-unrelated function of MCL-1 and its physiological role that could critically lead to MCL-1 inhibitor development.