Hypoxia and immune-suppressive microenvironments in glioblastoma drive transcriptional plasticity and phenotypic transition. Understanding these processes is crucial for overcoming therapy resistance and tumor relapse. This study investigates the expression pattern of sterile alpha motif domain-containing 9 (SAMD9) under these conditions, evaluates its prognostic value and spatial distribution, and explores its therapeutic implications.

Umin was discovered in L. and/or L. C-curcumin and its derivatives, like synthetic cyclic C-curcuminoids, are promising anticancer compounds with exceptional pharmacokinetic profiles compared to curcumin.

Colorectal cancer (CRC) is the third most prevalent cancer and one of the leading causes of cancer-related mortality in the world. Early detection is crucial in preventing deaths, but current screening methods have various limitations. So today, much attention is focused on genetic changes, including mutations in oncogenes and tumor suppressor genes, and epigenetic modifications such as aberrant methylation and alterations in the expression of specific microRNAs that contribute to CRC development. This has led to the discovery of more specific and sensitive molecular biomarkers. Furthermore, the use of liquid biopsy, which has a high potential for identifying molecular tumor markers, provides a perspective for overcoming the limitations of conventional screening methods. In this review, we first discuss the intricate molecular processes involved in the development of colorectal tumors. We then delve into the concept of liquid biopsy, exploring its traceable components such as extracellular vesicles, circulating tumor cells, circulating tumor DNAs, and circulating tumor RNAs. We also examine various methods for analyzing these components to identify molecular biomarkers for CRC screening. Additionally, we refer to the development of new diagnostic kits for CRC, such as Epi proColon, ColoSure, and Cologuard, which offer non-invasive utilization of genetic and epigenetic biomarkers. Lastly, we address the current challenges faced in using these biomarkers in a clinical setting. Despite the obstacles, these non-invasive and reliable markers have the potential to enable early detection of CRC and likely increase screening uptake, potentially replacing current modalities.

We have recently identified transcription factor c-Myb as a negative prognostic factor in osteosarcoma (OSA) patients associated with metastatic disease. Transcriptomic analysis identified creatine kinase B (CKB) as one of the most deregulated genes in OSA cell lines with depleted MYB. CKB is a component of the creatine/phosphocreatine system that plays a key role in maintaining cellular energy homeostasis and energy transport to sites with high demand. This study was therefore conducted to investigate the functional significance of CKB in OSA.

Lung adenocarcinoma remains one of the most common causes of cancer deaths. The tumor grows by avoiding the immune system and adapting to stress in the endoplasmic reticulum. The IRE1α-XBP1 pathway is a key pathway for cells to sense stress in the endoplasmic reticulum and has a large effect on the immune system. PRKCSH encodes a regulatory subunit of glucosidase II that helps keep the endoplasmic reticulum in balance by modifying how IRE1α works. However, it is unclear how it affects tumor immunity. This study used clinical sample analysis, bioinformatic analysis, CRISPR/Cas9-mediated gene deletion, cytokine profiling, macrophage co-culture, and zebrafish xenograft experiments to investigate the immunological role of PRKCSH. PRKCSH deficiency reduced basal IRE1α phosphorylation but led to exaggerated activation under ER stress, including increased XBP1s and p-JNK signaling. IL-6 and IL-8 secretion was suppressed in PRKCSH-knockout (KO) cancer cells, disrupting cytokine-mediated immune suppression. Conditioned media from PRKCSH-KO cells enhanced M1 macrophage polarization in vitro, as evidenced by increased CD86⁺ macrophages and expression of key M1-polarization markers. These effects were corroborated in zebrafish xenografts, where PRKCSH deficiency diverted the immune environment toward an M1-dominant phenotype. Analysis of clinical pleural effusion samples further validated these findings, revealing a significantly reduced M1/M2 macrophage ratio in malignant versus benign conditions. Furthermore, PRKCSH-KO cells exhibited increased susceptibility to ER stress-induced apoptosis and ferroptosis, along with impaired autophagy. In conclusion, our findings place PRKCSH as a key regulator linking ER stress signaling with tumor immune evasion and cell death pathways. Targeting PRKCSH may represent a promising therapeutic strategy to promote ferroptosis and anti-tumor immunity in lung adenocarcinoma.

Solid-type adenoid cystic carcinoma (ACC) is the most aggressive pathological type with the poorest prognosis. Extensive neovascularization and recruitment of cancer associated fibroblasts (CAFs) are the main characteristics, but the relationship between the two remains unclear.

Natural killer (NK) cells represent a fundamental aspect of the innate immunity. These cells considered as a vital part of tumor immunosurveillance by directly eliminating cancer cells and releasing cytokines. Their role is closely controlled through the equilibrium between activating and inhibitory signals. MicroRNAs (miRNA), being short non-coding RNAs, involve in controlling the differentiation, maturation, and effector responses of NK cells. Here, we highlight the functions of miRNAs in controlling NK cell lineage commitment, subset differentiation, cytotoxicity, and immune checkpoint expression. Additionally, it explores how tumor-derived factors, such as hypoxia, modulate miRNA expression, thereby impairing NK cell activity within the tumor microenvironment (TME). Additionally, we summarized how manipulating miRNA pathways could improve NK cell-based immunotherapies.

CAR T cells still face numerous obstacles in treating hematologic and solid malignancies. Although gene editing technologies have improved CAR T cell therapy, there are currently no systematic reviews to broadly address preclinical and clinical outcomes of gene-edited CAR T cells. Therefore, we aimed to systematically review the preclinical and clinical studies that evaluate the outcomes of knocked-out/knocked-down (KO/KD) CAR T cells.

The reprogramming and polarization of cells within the tumor microenvironment (TME) are fundamental processes that critically influence the dynamics of tumor progression and response to therapy. These processes can either promote tumor evasion and metastasis or mount effective anti-tumor responses, thereby determining the overall tumor landscape. At the center of this dynamic interplay are exosomes that facilitate crucial intercellular communication by transferring bioactive molecules such as proteins, lipids, and nucleic acids. While the roles of individual TME components in cancer progression have been extensively characterized, the precise mechanisms through which the reprogramming of these elements favors tumor advancement remain inadequately elucidated. This review investigates the complex functions of exosomal signaling in the reprogramming and polarization of TME constituents, highlighting their dual capacity to orchestrate tumor-promoting and tumor-suppressing signals. This synthesis aims to elucidate how the modulation of TME cell behavior impacts cancer progression and contributes to the broader understanding of tumor biology.

This study employed non-targeted liquid chromatography-mass spectrometry (LC-MS) to investigate the salivary metabolomic profiles of 177 participants, including 147 patients with gastric cancer (GC) and 30 controls with common gastritis. Following rigorous quality control measures, a total of 333 high-confidence metabolites were identified from an initial pool of 368 positive-mode metabolites and 178 negative-mode metabolites. Principal component analysis (PCA) and linear discriminant analysis (LDA) revealed significant differences between the GC and control groups, with stage I GC clearly distinguishable from more advanced stages. Differential metabolite screening was conducted using partial least squares discriminant analysis (PLS-DA) in conjunction with t-tests and fold-change analysis. After controlling for confounding factors such as age, smoking, and alcohol use, 38 salivary metabolites were identified as potential diagnostic markers. Notably, the univariate and multivariate diagnostic models demonstrated excellent discriminative performance in distinguishing GC patients from controls. PLS-DA validated by permutation testing, along with univariate and multivariate ROC analyses, exhibited excellent classification performance based on the 38 salivary metabolites. Metabolic analysis revealed significant downregulation of purines, pyrimidines, amino acids, and carbohydrates in the saliva of GC patients, while sebacic acid and GABA were found to be upregulated. Tyrosine was identified as the most significantly altered metabolite between early and advanced stages of GC. These findings underscore the substantial impact of gastric cancer on the salivary metabolome and suggest the potential of saliva as a promising tool for mass screening of GC.Trial registration DGLES, NCT01420588, Registered 19 August 2011, https://clinicaltrials.gov/ct2/show/NCT01420588.

Glioblastoma multiforme (GBM) is an aggressive brain tumor with poor response to chemotherapy such as Carboplatin, mainly due to drug resistance and systemic toxicity. Recent studies suggest that probiotics like Bifidobacterium reuteri may have anti-tumor properties and enhance the efficacy of chemotherapy. This study evaluates the potential of B. reuteri Ab.338 SH (GenBank: PV961363), isolated from traditional yogurt, in potentiating Carboplatin's effects on U-87 MG glioblastoma cells.

Cancer stem cells (CSCs) are essentially linked with the pathogenesis of human cancers. It has been reported that RNA binding protein modulates the stemness of CSCs. This investigation identified that in CSCs, NOVA1 is upregulated. Knockdown of NOVA1 inhibits tumorigenesis and self-renew ability of liver CSCs, whereas its forced expression has opposite effects. The mechanistic analysis revealed that in liver CSCs, SOX4 is a direct NOVA1 target. It enhances tumorigenesis and self-renew ability of liver CSCs by increasing SOX4 mRNA stability by combing with the 3-'UTR. Furthermore, NOVA1 overexpression desensitizes hepatocellular carcinoma (HCC) cells to Lenvatinib-mediated cell development suppression and apoptosis. Patients' cohort analysis indicated that low NOVA1 might predict the benefits of Lenvatinib in HCC individuals. Moreover, knocking down SOX4 could reverse the NOVA1 overexpression-mediated desensitization of HCC cells to Lenvatinib-induced cell apoptosis. In summary, this investigation indicates the essential role of NOVA1 self-renew of CSCs and tumorigenesis in the liver, suggesting it as an optimal HCC therapeutic target.

Bladder cancer (BCa) is a prevalent malignancy and major cause of cancer-related mortality in men, with clinical outcomes still varying despite advances in personalized treatments. High inter- and intra-tumor heterogeneity significantly contributes to this variability. While traditional high-throughput sequencing has provided insights into BCa mechanisms, driver genes, and clinical strategies, it falls short in completely elucidating cellular heterogeneity. Recently, single-cell sequencing (SCS) technologies have substantially enhanced the detection of tumor heterogeneity by improving sensitivity, accuracy, and efficiency. Single-cell transcriptome sequencing offers unbiased, high-resolution analysis of gene expression patterns at the single-cell level, offering essential insights into BCa pathogenesis. This article reviews advancements in SCS technology and its applications in evaluating tumor heterogeneity, the tumor microenvironment, metastasis, and treatment resistance, offering new perspectives for future BCa research.

Hepatocellular carcinoma (HCC), a highly aggressive primary liver cancer, exhibits unclear heterogeneity in RNA-binding protein (RBP) expression dynamics. This study investigates single-cell-level RBP heterogeneity, regulatory roles in HCC progression, and their therapeutic potential.

Neoadjuvant immunotherapy (NIT) has emerged as a transformative treatment strategy across various cancer types. However, due to the significant heterogeneity of tumors, patients exhibit highly variable responses to NIT, making the accurate preoperative identification of those who would benefit a pressing clinical challenge. In recent years, artificial intelligence (AI), particularly machine learning (ML) and deep learning (DL), has opened new pathways for predicting treatment response. AI-driven approaches have the ability to extract latent features from high-dimensional, multimodal oncological data, facilitating the construction of efficient predictive models that can optimize individualized treatment strategies. In this review, we systematically summarize existing AI-driven computational approaches for NIT response prediction, categorizing them into indirect and direct predictive paradigms. The indirect paradigm predicts clinically validated surrogate biomarkers to infer therapeutic response to NIT. In contrast, the direct paradigm leverages AI to analyze high-throughput data and establish data-driven biomarkers that directly predict clinical endpoints of NIT. Additionally, we categorize existing AI predictive models based on data modalities, spanning radiomics, pathomics, genomics, and multi-omics approaches, each providing distinct insights into tumor characteristics and treatment response. Despite notable progress, current predictive models still face significant challenges, which we broadly classify into biomarker-based and AI-based limitations. We further discuss potential strategies to address these challenges. This review systematically summarizes recent AI-based predictive models for NIT response across cancer types. By offering a structured analysis of current methodologies and challenges, we aim to guide future research and accelerate the integration of AI into precision immunotherapy.

Cancer stem cells (CSCs) represent a resilient subpopulation within tumors, capable of driving progression, metastasis, and recurrence. One mechanism that enables this plasticity is asymmetric cell division (ACD), a process by which CSCs generate both a self-renewing stem cell and a differentiated daughter cell. While traditionally associated with tissue development, ACD is now recognized as a dynamic and regulated feature of cancer biology, particularly in response to stress conditions such as hypoxia and radiation. In this review, we provide a comprehensive and mechanistic synthesis of how intrinsic factors such as polarity complexes, cell fate determinants (CFDs), spindle orientation cooperate with extrinsic cues from the tumor microenvironment to orchestrate ACD in CSCs. We explore how this process contributes to tumor heterogeneity, therapy resistance, and the emergence of quiescent, drug-tolerant CSCs across multiple malignancies, including brain, breast, colorectal, and hematologic cancers. Importantly, we highlight recent efforts to pharmacologically disrupt or redirect ACD using inhibitors of NOTCH, WNT, AURORA kinases, and MSI1, presenting ACD as a therapeutic vulnerability rather than a static trait. By shifting the focus from CSC markers to division mode, this review introduces a novel conceptual framework for targeting tumor hierarchy and plasticity. Understanding and manipulating ACD offers a promising frontier in precision oncology - one where altering the balance of cell fate decisions could limit relapse, reduce intratumoral complexity, and enhance long-term treatment outcomes.

Glioblastoma multiforme (GBM) is a highly aggressive brain tumor often treated with Temozolomide (TMZ). Research reveals that secretory substances and receptor-activated signaling may contribute to TMZ resistance in GBM cells. RNA-Seq and bioinformatics analyses reveal that TMZ treatment downregulates most genes, particularly those involved in cell structure and metabolism, while activating genes linked to secretory substances like cytokines, chemokines, and growth factors. Antibody array analysis identified a significant increase in TGF-α secretion after TMZ treatment, which also triggered its associated pathways. Moreover, the remarkable secretion of TGF-α also triggered the activation of its associated pathways. Notably, a marked increase in TGF-α expression was observed in TMZ-resistant cells. TGF-α knockdown restored TMZ sensitivity in a mouse xenograft model. Tissue analysis revealed significantly higher TGF-α levels in GBM, suggesting its potential as a drug resistance biomarker and target for new therapies.

Small cell lung cancer (SCLC) is a highly aggressive malignancy with limited therapeutic options. Triptolide (TPL), a natural compound derived from the traditional Chinese herbal medicine Tripterygium wilfordii Hook F., exhibits broad antitumor effects. However, its role in SCLC remains unexplored.

Breast cancer is the most common cancer among women, and metastasis is the leading cause of mortality. It is still unknown how breast cancer cells metabolically adapt to successfully metastasize to different organs to survive adverse conditions, including varying nutrient availability. The purpose of this study is to elucidate the metabolic characteristics and glucose adaptation mechanisms of breast cancer cells that preferentially metastasize to the lungs or the liver.

Kv10.1 potassium channel has been shown to be involved in breast cancer luminal cell proliferation and survival as well as migration in basal cell model in normoxia. Moreover, it is clearly established that solid tumors present a hypoxic center. Currently, few information is available about the involvement of the Kv10.1 channel in hypoxic context in breast cancer progression.