Advancements in cancer stem cell therapy: The effective integration of traditional Chinese medicine and nanotechnology.

Molecular insights for the tumor suppressor role of SPOP in prostate cancer.

Inhibition of PRMT5-dependent YAP methylation attenuates tumorigenicity and radioresistance in glioblastoma.

NSAIDs-loaded nanocarriers as emerging anticancer therapeutics: Harnessing inflammation-targeted drug delivery to combat tumor progression.

A comprehensive understanding of how diverse adult stem cell populations function in harmony is crucial for maintaining homeostasis and ensuring the normal functioning of body tissues. Two types of stem cells in adult tissues have attracted attention, including very small embryonic-like stem cells (VSELs) and multi-lineage differentiating stress-enduring cells (MUSE), reported for the first time in 2006 and 2010, respectively. VSELs are pluripotent stem cells developmentally linked to the primordial germ cells, while MUSE cells, initially described as multipotent, are now being defined as having pluripotent characteristics and further differentiate into MSCs. VSELs are the most primitive, virtually immortal and pluripotent stem cells that survive lifelong in all tissues in small numbers and undergo asymmetrical divisions to give rise to tissue-specific progenitors of different sizes and fates. VSELs are 5-7μm in size, spherical in shape, with a cell surface profile of LIN-CD133 + CD45- while MUSE cells are 10-15μm in size, with abundant cytoplasm, horseshoe/bean-shaped nuclei, cytoplasmic OCT-4 and are CD45+, like hematopoietic stem cells. In the mouse uterus, VSELs undergo cyclic changes in response to circulatory hormones, regenerate both the epithelial and stromal compartments in an atrophied uterus (upon bilateral ovariectomy, in the absence of macrophages) and also upon chronic injury. Exposure to endocrine-disrupting chemicals disrupts the functions of VSELs and results in various pathologies, including endometrial cancer. The crucial role of dysfunctional VSELs resulting in cancer initiation, progression, metastasis and recurrence was recently discussed. On the other hand, multiple clinical trials have reported the potential of MUSE cells for ensuring regeneration upon transplantation. VSELs regenerate damaged and diseased tissues when a healthy paracrine support is provided by the transplanted MUSE cells/MSCs; however, remain elusive due to their small size and scarce nature. In summary, the view that MUSE cells phagocytose damaged cells and subsequently differentiate into the same cell type is fundamentally challenged and requires careful re-evaluation.

Accumulating evidence indicates that environmental exposures, particularly to nitrites, play a critical role in the initiation and progression of gastric cancer (GC). During carcinogenesis, exosomes act as key mediators of intercellular communication. Exosomes derived from N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced malignantly transformed GES-1 cells (TGES-1), as well as serum exosomes from gastric cancer patients with a history of high nitrite exposure, were found to influence normal cells and promote GC initiation. The present study established a malignant transformation model and applied bioinformatics analyses to screen and validate candidate circRNAs. A series of functional and mechanistic experiments were performed to elucidate the regulatory role of exosomes in GC progression. Circ0000549 was markedly upregulated in MNNG-exposed GES-1 cells, their derived exosomes and serum exosomes from patients with GC. Further investigations revealed that circ0000549 overexpression enhanced GES-1 cell malignant features, while also modulating epithelial-mesenchymal transition and stemness-related properties. Nude mouse experiments demonstrated that circ0000549, carried by malignantly transformed exosomes, plays a crucial role in MNNG-induced gastric carcinogenesis. Mechanistically, miR-15b-5p was identified as a potential target of circ0000549. Circ0000549 functioned as a sponge for miR-15b-5p, leading to increased KIF1B expression and subsequent activation of the PI3K/AKT signaling pathway. Collectively, these findings reveal that exosomal circ0000549 promotes malignant transformation of GES-1 cells through the miR-15b-5p/KIF1B/PI3K/AKT axis. Exosomal circ0000549 may serve as a promising biomarker for GC diagnosis and prognosis, highlighting its potential as a target for future therapeutic investigation.

Early-onset colorectal cancer in Argentina: a multicenter surgical analysis of incidence, stage, and metastatic patterns

Introduction Cancer imposes a substantial burden characterized by high morbidity and mortality, reduced quality of life, and increased healthcare costs. This burden is expected to rise due to aging populations and persistent exposure to risk factors. Although emerging cancer technologies hold promise for improving clinical and economic outcomes across the care continuum, translating research findings into routine clinical practice remains a major bottleneck. The European Commission has prioritized addressing this challenge by fostering the rapid adoption of safer and more effective interventions. As part of its strategic plan, the European Union (EU) has launched research and innovation initiatives aimed at integrating cancer genomic technologies into public health and clinical systems. The CAN.HEAL evaluation framework presents a structured approach to classifying innovative cancer-related interventions by maturity level and to guide researchers and decision makers in supporting adoption and scale-up efforts. Methods The evaluation framework was developed within the CAN.HEAL consortium, under the EU strategic cancer initiative that funded this research and innovation action, and agreed upon a consensus-based, iterative methodology including the stakeholders perspectives. Key steps included landscape analysis, identification of key actions, structured discussions, expert consultations, and pilot testing of the assessment tool. The selected dimensions-grounded in equity, early health technology assessment (HTA), and innovation adoption principles-were hierarchically organized into subdomains, domains, and three overarching dimensions. A two-step scoring system was used to assess each key actions across planning/definition and execution stages, with weighted final scores. The CAN.HEAL evaluation framework defines three adoption-readiness levels, ranging from implementation at the healthcare provider level to integration across multiple healthcare systems. A structured 71- key actions assessment tool, organized into three dimensions, was used to determine each intervention level: (1) equity-capacity building, research equity, and access; (2) impact assessment-early clinical development, cost considerations, and broader value; and (3) implementation, adoption, and scale-up readiness-desirability, feasibility, and viability from developer and adopter perspectives, including reimbursement pathways. Conclusion The CAN.HEAL evaluation framework is designed to offer a systematic, evidence-informed approach to assessing the adoption readiness of cancer-related innovations. Further validation in cross-border, real-world settings is needed to ensure practical utility and scalability.

Understanding which driver mutations are required for cancer initiation, maintenance, or both phases remains poorly understood. In this study, we uncover that highly prevalent preleukemic DNMT3A mutations are only required during disease initiation but become dispensable after leukemic transformation, uncovering the context-specific role of this driver mutation with important therapeutic implications. See related commentary by Zhou and Huang, p. 428.

Cancer is a global health challenge. The initiation and progression of cancer are correlated with dynamic dysregulation of RNA regulatory networks. This review systematically explains how contending RNAs (including mRNA, miRNA, lncRNA, circRNA, etc.) remold gene expression programs across multiple dimensions. They do this primarily through the competing endogenous RNA sponge effect, RNA-protein complex assembly, RNA editing (A-to-I editing, m6A modification, etc.), tumorigenesis, heterogeneous evolution, and therapeutic resistance. RNA regulatory networks do not only help one to decode cancer biology but because they are dynamic in nature, they are now also being looked at as good precision targets for diagnosis and treatment. This article integrates recent findings on the emerging functions of RNA networks in tumor metabolic reprogramming, tumor immune microenvironment shaping, and cancer stem cell property maintenance, while highlighting their clinical application prospects as liquid biopsy biomarkers. Our therapies focus on assessing the potential and clinical translation bottlenecks of novel RNA-targeted interventions, including antisense oligonucleotides, RNA aptamers, and the CRISPR-Cas13 system. A dynamic adjustability made the RNA-targeted therapies promising intervention nodes in precision medicine even if most of them are still in a preclinical state.

In 2022, Hanahan integrated polymorphic microbiomes to the hallmarks of cancer, resulting in 14 overarching features that are considered fundamental to initiation and progression of cancers. It is well acknowledged that genomic instability/genetic alterations together with tumor-associated inflammation are so called "enabling hallmarks" as they drive the acquisition of the other traits. The microbiome is a key component of the inflammatory tumor stroma. Pancreatic ductal adenocarcinoma (PDAC) in particular is characterized by a pronounced stromal compartment whose role in the acquisition of malignant properties is well documented. Recent studies indicate massive alterations of the microbiome in PDAC tissues compared to healthy pancreas or precursor lesions. However, the mechanistic role of the PDAC-associated microbiome, its influence on the hallmarks of cancer, and how this relates to PDAC malignancy remain poorly understood. This raises the question of whether the tumor-associated microbiome through its direct influence on PDAC cells, their precursors, and the surrounding non-neoplastic cells promotes the acquisition of other hallmarks that drive PDAC development and progression. This perspective article outlines the current knowledge of the impact of the PDAC-associated microbiome on the hallmarks of cancer in PDAC. These current findings support the altered microbiome as a third enabling hallmark of PDAC and emphasize that further mechanistic studies are urgently needed to further substantiate its fundamental importance for this tumor entity. This knowledge will provide the basis for clinical translation to develop more effective therapeutic approaches for PDAC. The intratumoral microbiome in PDAC exhibits numerous interactions with the hallmarks of cancer. Hallmarks indicated in blue have demonstrated interactions with the microbiome, while others still remain underexplored. These extensive interactions substantiate the role of the intratumoral microbiome in PDAC as an enabling hallmark, underlining its potential as a therapeutic target. Partially created with biorender.com.

Dual-mode biosensors based on upconversion nanoparticles and quantum dots combined with a signal amplification strategy for the detection of miRNAs.

Micro- and nano-plastics (MNPs) are small plastic particles generated from the fragmentation of larger plastic products, which are widely manufactured and often improperly discarded. Because MNPs are not fully degradable, they persist and accumulate across all ecosystems, contributing to global environmental concerns. The detection of MNPs within the food chain and in various human tissues and biological samples has raised pressing questions about their potential health risks. Cellular exposure to MNPs induces molecular, metabolic, and biological changes that may culminate in pathological outcomes. Given the chronic, lifelong exposure to escalating doses of MNPs, their involvement in the initiation and progression of human cancers is increasingly suspected. Clinical and experimental studies support this hypothesis, although clear causal evidence is still lacking. To address this gap, research in recent years has expanded rapidly, generating a growing body of literature on MNPs and cancer. In this review, we provide an up-to-date and critical overview of the data linking MNPs exposure to human cancer. We analyze the molecular and biological mechanisms potentially underlying MNP-induced carcinogenesis, with emphasis on the main routes of human exposure and tissue-specific effects. Particular attention is given to neoplastic conditions arising in primary contact sites (gastrointestinal tract, lung, and skin) and secondary targets (liver, kidney, brain). Finally, we highlight key knowledge gaps and propose future research directions to advance this emerging field. Based on the oncogenic potential of MNPs, an exhaustive and stringent scrutiny of the most recent findings will help scientists drawing solid conclusions in this highly debated area.

Myotubularin-related proteins (MTMRs) comprise a family of lipid phosphatases using phosphatidylinositol 3-phosphate and phosphatidylinositol 3,5-bisphosphate as their substrate. Several members have a well-established role in the pathogenesis of human myopathies and neuropathies. There is a growing body of evidence that the portfolio of diseases where MTMRs play a role should be extended to cancer. MTMRs are thus closing the gap on their functional counterparts, the phosphatidylinositol kinases. MTMRs do not contribute to cancer initiation through driver mutations, but their expression in tumours is frequently altered, leading to defects in cell proliferation, migration or cell death. In some instances, MTMR misexpression contributes to resistance to cancer treatment. In this review we summarize the current knowledge with the emphasis on the molecular mechanisms underlying the MTMR function in cancer pathogenesis.

SERS-enabled immune monitoring: Decoding the tumor microenvironment for precision Cancer immunotherapy.

Key signaling pathways in the development and progression of prostate cancer: The crosstalk between inflammation, autophagy, and pyroptosis.

Cancer is driven by genomic lesions and malignancy-promoting transcriptional programs. In blood cancers, both are often interconnected as lesions frequently affect transcription factor (TF)-encoding genes. TFs largely function through enhancers, and enhancer deregulation is linked to cancer initiation and progression. Consequently, enhancer-targeting drugs are in trials for several advanced hematologic cancers. However, for cancers not driven by TF-related lesions, it is less clear how their transcriptional programs are established; if oncogenesis involves enhancer-deregulation, and if they are sensitive to therapeutic enhancer-targeting. Here, we explore this for Philadelphia chromosome-positive (Ph+) B-lineage leukemia (B-ALL), the most common B-ALL in adults with a historically poor prognosis. Ph+B-ALL is driven by BCR::ABL1, a kinase without TF-related function. We report that malignant transformation and transcriptional reprogramming by BCR::ABL1 is indeed defined by enhancer reprogramming and that enhancer signatures differentiate Ph+B-ALL from other leukemias. Mechanistically, we show that BCR::ABL1 itself induces enhancer activation, through its kinase activity and via kinase-dependent activation of STAT5, ETV5, and MYC. Consequently, BCR::ABL1-induced genes are hypersensitive to enhancer inhibition, and Ph+B-ALL cells are hypersensitive to enhancer-targeting drugs. Enhancer-targeting further improves the efficacy of BCR::ABL1 kinase inhibitors used for Ph+B-ALL therapy, especially in cells from IKZF1PLUS patients that most frequently relapse from current treatment, suggesting enhancer-targeting as a potential promising addition to current therapy.

Processed meat contains multiple substances with mutagenic properties, but there is limited knowledge about the combined effect of polycyclic aromatic hydrocarbons (PAHs) and N-nitroso compounds (NOCs). This study characterized the carcinogenic potential of single or combined dietary exposure to Benzo[a]pyrene (BaP, a PAH) and a mixture of six food-derived NOCs in the A/J Min/+ mouse model for human colorectal cancer. Mice were given diets containing low or high concentrations of BaP and/or NOCs for nine weeks. The concentrations were based on estimated daily intake levels in the European population. A sex-dependent increased CRC initiation was detected after combined exposure to the high doses of BaP and NOCs. No effects were seen on CRC following exposure to the low doses of BaP or NOCs individually or in combination. Targeted plasma metabolomics revealed alterations in cellular membranes, lipid and energy metabolism in mice exposed to the high doses of BaP and NOCs. An alteration of plasma metabolites was also seen in mice exposed to the low dose of BaP, but not in mice exposed to the low dose of NOCs or to the combined low doses of BaP and NOCs. The study highlights the complex interplay between dietary carcinogens.

The epigenetic modification of transfer RNA (tRNA) and tRNA-derived small RNAs (tsRNAs) is associated with the initiation and development of cancer. However, the biological role of m5C-modified tsRNAs, especially in bladder cancer (BC), and their regulatory mechanisms remain unclear. Here, we identify a novel m5C-modified tsRNA, m5C-tRF3b-CysGCA-23 (mtRC), whose expression is significantly downregulated in both tumor tissues and urine samples of BC patients and is strongly negatively correlated with the malignant progression of bladder cancer. In vitro and in vivo functional experiments reveal that mtRC, but not its unmodified counterpart (tRC), exhibits a tumor-suppressive role. Furthermore, NOP2/Sun RNA methyltransferase 6 (NSUN6) regulates mtRC abundance and suppresses cell proliferation. Mechanistically, mtRC directly binds the oncosuppressor protein RNA-binding motif 4 (RBM4) and improves its stability by preventing RBM4 ubiquitination, thereby upregulating RBM4 protein levels. RBM4 reduces the levels of glycolytic genes and decreases glycolysis, thereby inhibiting histone H3 lysine 18 lactylation (H3K18la). This reduction in H3K18 lactylation attenuates the transcriptional activation of the downstream oncogenes IL1RAP and VASH2, thereby ultimately suppressing tumor malignancy in BC. Together, our results not only underscore the critical role of mtRC in BC but also unravel a novel and coherent regulatory signaling axis-mtRC/RBM4/H3K18la/IL1RAP&VASH2-that orchestrates BC malignancy, suggesting mtRC may serve as a candidate therapeutic target for BC treatment.

BackgroundOmics, encompassing genomics, transcriptomics, proteomics and metabolomics, plays a pivotal role in elucidating the molecular mechanisms underlying lung cancer and advancing precision oncology. While existing studies have primarily focused on the technical development and clinical efficacy of omics applications in cancer, there remains a notable gap in comprehensive assessments of the global research landscape. At different stages of lung cancer initiation, progression, and metastasis, genomics and transcriptomics predominantly reveal oncogenic alterations and dysregulated signaling networks, whereas proteomics and metabolomics capture functional protein dynamics and metabolic reprogramming that drive tumor growth and metastatic adaptation. Importantly, the integration of multi-omics data enables a systematic understanding of the crosstalk between genetic alterations, transcriptional regulation, protein expression, and metabolic remodeling throughout lung cancer evolution. This bibliometric analysis study aims to systematically evaluate scientific output, research trends and hotspots in omics-related lung cancer research.MethodsRelevant publications were retrieved from the Web of Science Core Collection (WoSCC) from January 1, 2004 to April 27, 2024. Bibliometric analyses and knowledge domain visualizations were conducted using VOSviewer (v1.6.20), CiteSpace (v6.3), R (v4.3.3), and Origin (2024).ResultsA total of 19,087 publications were included, demonstrating sustained growth over two decades [2004–2024]. China contributed the largest volume of publications, whereas the USA showed higher citation impact and stronger influence in collaboration networks. Keyword co-occurrence and burst analyses illustrated that “expression”, “lung cancer”, “gene expression”, “tumor microenvironment”, “mutation” and “immunotherapy” are dominant and emerging themes. These findings indicate a clear shift from single-omics approaches and gene-centric investigations toward integrative multi-omics frameworks, with increasing emphasis on the tumor microenvironment (TME) and immunotherapy. The burst analysis of keywords also highlights the rising prominence of artificial intelligence (AI) and machine learning (ML), which have emerged as rapidly growing methodological backbones in recent years.ConclusionsResearch on omics in lung cancer has rapidly evolved toward integrative, TME-focused and immunotherapy-oriented paradigms, with AI/ML serving as an enabling analytical infrastructure. This study underscores the critical role that omics in facilitating early detection, guiding personalized therapeutic strategies, and improving prognostic accuracy. The findings suggest that enhancing cross-disciplinary collaboration and accelerating the clinical translation of multi-omics data may help overcome current challenges in precision oncology.