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.

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.

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.

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.

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.

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.

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.

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.

Circular RNAs (circRNAs), a unique class of non-coding RNAs, have gained attention due to their stable closed-loop structure and involvement in diverse cellular processes. Their remarkable stability and abundance in biological fluids, particularly when encapsulated within exosomes, make them highly promising candidates for clinical applications. This review offers a detailed insight into the growing field of exosomal circRNAs, starting with the fundamental principles of circRNA biogenesis and the selective mechanisms governing their sorting into exosomes. We explore the complex regulatory network controlled by circRNAs, highlighting their roles as microRNA (miRNA) sponges, interactors with RNA-binding proteins (RBPs), regulators of transcription and RNA stability, and even as templates for translating into novel peptides or proteins. We elucidate how these actions are mediated by exosomal circRNAs when delivered to recipient cells, influencing the behavior of target cells. The review critically evaluates the current and emerging methodologies for the detection, quantification, and functional analysis of exosomal circRNAs. We extensively discuss the clinical implications, highlighting the significant potential of exosomal circRNAs as non-invasive biomarkers for the diagnosis, prognosis, and monitoring of various diseases, with a particular focus on cancer. Furthermore, we explore their therapeutic landscape, including strategies for targeted delivery, their role in modulating drug resistance, and their intricate functional crosstalk with other non-coding RNAs in cancer progression. While recognizing the promising potential of exosomal circRNAs, we also address the existing technical challenges and highlight the future directions needed to leverage their diagnostic and therapeutic applications. Our review highlights the significance of interpreting the circular code of exosomal circRNAs as a vital step toward achieving the objectives of precision medicine.

For patients with advanced hepatocellular carcinoma, sorafenib is considered a highly effective targeted molecular drug; however, sorafenib resistance limits its therapeutic efficacy. Hepatocellular carcinoma, a type of solid tumour, contains hypoxic and oxygen-rich regions within its internal structure. This study investigated the mechanism by which hypoxic hepatocellular carcinoma cells influence the sorafenib sensitivity of normoxic hepatocellular carcinoma cells through the secretion of hypoxic exosomes containing miRNA signals.

Pegaspargase is a pegylated asparaginase formulation used in hematological malignancies. However, its application in solid tumors is greatly limited due to inherent drug resistance nature of solid tumors. Poor prognosis and lack of effective treatment options for pancreatic cancer urgently necessitate the exploration of novel therapeutic approaches. In the present study, we analyzed pegaspargase's cytotoxicity on pancreatic cancer cells (SU.86.86 and BxPC-3) in vitro. Then we evaluated the level of autophagy and related pathway proteins during treatment. Finally, we aimed to evaluate the effect of autophagy modulator on pegaspargase efficacy both in vitro and in vivo. The results revealed that pegaspargase (4 IU/mL) decreased the viability of SU.86.86 and BxPC-3 cells and induced apoptosis rates of 28.7% and 16.9%, respectively. Pegaspargase activated autophagy and downregulated Akt/mTOR path-way. Furthermore, autophagy inhibitors increased the cytotoxicity of pegaspargase (4 IU/mL) on SU.86.86 and BxPC-3 cell lines and induced apoptosis rates of 39.9% and 21.9%, respectively. In vivo evaluation confirmed that autophagy inhibition enhanced the antitumor efficacy of pegaspargase. In conclusion, our research demonstrated that combining pegaspargase with autophagy inhibition is a promising approach in pancreatic cancer clinical treatment.

Endometrial Cancer is a prevalent malignant tumor in gynecology, marked by high incidence and poor prognosis. The discovery of cuproptosis, a copper-dependent cell death pathway, offers new therapeutic potential. We systematically reviewed literature on cuproptosis mechanisms in endometrial cancer, including copper metabolism dysregulation, prognostic biomarkers, and therapeutic strategies. Then we identified three key findings: (1) Copper homeostasis disruption promotes cancer via angiogenesis, metastasis, and chemoresistance; (2) Cyclin-dependent kinase inhibitor 2 A and glutaminase exhibit strong prognostic predictive value; (3) The strategy of regulating copper homeostasis exhibits anticancer effects. Cuproptosis targeting represents a promising strategy for endometrial cancer management. Further clinical validation of cuproptosis-related biomarkers and optimization of combination therapies are warranted.

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.

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.

Immunotherapies change the paradigm of current pulmonary oncological clinics, although majority of patients fail to benefit from these treatment modalities. HAT1 overexpression is frequently diagnosed in lung cancer patients. Effective immunotherapeutic scheme remains to be determined for this portion of patients.

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.