Molecular alterations of muc1 and their therapeutic exploitation: Emerging opportunities in cancer therapy.

Molecular regulation of telomeric elongation and TERT splicing in planarians.

c-Myc: Central regulator of autophagy and senescence in cancer.

Circular RNAs (circRNAs) perform critical functions in cancer biology, commonly serving as microRNA (miRNA) sponges to modulate gene expression. Nevertheless, their participation in gut microbiota-driven colorectal cancer (CRC) has yet to be substantially investigated. Fusobacterium nucleatum (F. nucleatum), a well-recognized oncogenic bacterium in the human gut, has been implicated in CRC development, but the underlying mechanisms are not fully defined. In this study, we identified a novel circRNA, circPTBP3, which is the most significantly upregulated circRNA upon F. nucleatum infection, and is significantly upregulated in CRC tissues. CircPTBP3 is preferentially transcribed over its host gene PTBP3 in response to F. nucleatum through activation of the transcription factor ETS1. Functional assays demonstrated that circPTBP3 enhances CRC cell proliferation and tumor growth in vitro and in vivo. Mechanistically, circPTBP3 acts as a molecular sponge for miR-760, thereby relieving its suppression of the downstream target gene PUM1. In clinical CRC specimens, circPTBP3 expression showed a positive correlation with F. nucleatum abundance, PUM1 expression, larger tumor sizes, advanced TNM stages, and a negative correlation with miR-760 levels. These findings establish for the first time that circPTBP3 functions as a pivotal mediator of F. nucleatum 's oncogenicity, and reveal a novel F. nucleatum-circPTBP3-miR-760-PUM1 regulatory axis that promotes CRC progression. CircPTBP3 may serve as a potential biomarker and therapeutic target in F. nucleatum-associated colorectal carcinogenesis.

The role of lactic acid metabolism in anti-tumor immunity.

Interleukin-8: a tumor-agnostic biomarker integrating cancer biology and host response across solid tumors.

Quantum machine learning (QML) is rapidly transitioning from theoretical promise to practical relevance across data-intensive scientific domains. In this review, we provide a structured overview of recent advances that bridge foundational quantum learning principles with real-world applications. We survey foundational QML paradigms, including variational quantum algorithms, quantum kernel methods, and neural-network quantum states, with emphasis on their applicability to complex quantum systems. We examine neural-network quantum states as expressive variational models for correlated matter, non-equilibrium dynamics, and open quantum systems, and discuss fundamental challenges associated with training and sampling. Recent advances in quantum-enhanced sampling and diagnostics of learning dynamics, including information-theoretic tools, are reviewed as mechanisms for improving scalability and trainability. The review further highlights application-driven QML frameworks in drug discovery, cancer biology, and agro-climate modeling, where data complexity and constraints motivate hybrid quantum–classical approaches. We conclude with a discussion of federated quantum machine learning as a route to distributed, privacy-preserving quantum learning. Overall, this review presents a unified perspective on the opportunities and limitations of QML for complex systems.

Microplastic (MP) pollution and the rising global incidence of prostate cancer (PC) represent converging public health challenges, yet the potential contribution of MPs to organ-specific carcinogenesis remains poorly defined. Although MPs are recognized as systemic environmental hazards, their relevance to prostate cancer biology has not been comprehensively synthesized. This review examines evidence from environmental toxicology and oncology literature suggesting that MPs can accumulate in human prostate tissue, with higher burdens reported in malignant compared with benign samples in observational studies, though whether this reflects a causal relationship or differential retention in tumor tissue remains under investigation. Beyond acting as inert particulates, MPs possess a strong capacity to adsorb and transport endocrine-disrupting and pro-carcinogenic pollutants, including bisphenols, phthalates, polycyclic aromatic hydrocarbons (PAHs), and per- and polyfluoroalkyl substances (PFAS), thereby increasing localized toxicant exposure within this hormone-sensitive organ. We integrate current mechanistic evidence to propose a coherent framework in which MP-associated pollutants may converge on key molecular processes implicated in prostate carcinogenesis, including modulation of androgen receptor signaling, induction of oxidative stress and DNA damage, and activation of chronic inflammatory pathways. These interconnected processes are conceptualized as a 'triad of toxicity' that provides biological plausibility for a potential role of MPs in prostate cancer development without implying established causality. In parallel, selected plant-derived phytochemicals are discussed as mechanistically aligned, hypothesis-driven candidates based on their documented anti-androgenic, antioxidant, and anti-inflammatory activities, rather than as proven countermeasures against MP-induced toxicity. By uniting environmental toxicology with molecular oncology, this review positions MP-associated pollutants as a plausible environmental risk factor within the multifactorial landscape of prostate cancer and frames phytochemicals as pathway-oriented research leads. The findings underscore the need for interdisciplinary investigation, improved analytical methodologies, and translational studies to clarify the role of microplastic pollution in prostate cancer etiology.

Skeletal muscle as an endocrine and paracrine organ in breast cancer biology: a narrative review.

Introduction. Anesthetic agents traditionally are recognized for reversibly suppressing neuronal excitability through ion channel modulation and membrane interactions. Emerging evidence suggests these agents also may influence cancer cell biology. Malignant cells exhibit increased cholesterol-rich lipid rafts and aberrant expression of voltage-gated sodium (NaV) channels, particularly neonatal splice variants, which together promote oncogenic signaling, invasion, metabolic reprogramming, and metastasis. Because anesthetics directly interact with both lipid membranes and NaV channels, they may modulate cancer-specific vulnerabilities. Methods. Authors conducted a narrative using PubMed to identify experimental and clinical studies evaluating the effects of local, volatile, and intravenous anesthetics on lipid raft organization, NaV function, and cancer biology. Key search terms included “anesthetics,” “lipid rafts,” “voltage-gated sodium channels,” and “cancer.” Relevant mechanistic and preclinical data were synthesized. Results. Preclinical evidence demonstrates that local anesthetics inhibit NaV activity, reduce persistent sodium influx, impair cytoskeletal remodeling, suppress extracellular acidification, and decrease cancer cell migration and invasion. They also induce mitochondrial dysfunction, apoptosis, autophagy, and immunogenic cell death. In contrast, volatile anesthetics often activate PI3K/Akt/mTOR and hypoxia-inducible factor pathways while suppressing anti-tumor immunity. Intravenous agents such as propofol exhibit context-dependent effects, with studies demonstrating both anti-proliferative and pro-migratory outcomes. Conclusions. Anesthetics exert convergent effects on membrane lipid organization and NaV signaling, two interconnected regulators of malignant behavior. Local anesthetics demonstrate the most consistent anti-tumor profile, whereas volatile agents may promote survival signaling under certain conditions. Although clinical data remain largely neutral, these mechanistic insights provide a biologically grounded framework for interpreting perioperative oncologic outcomes and for designing anesthetic strategies that minimize tumor-promoting effects.

Mitochondria are central regulators of breast cancer progression and therapy response, acting beyond energy metabolism to integrate redox balance, regulated cell death, metabolic plasticity, and immune signaling. This review summarizes how mitochondrial metabolism, dynamics, stress signaling, and quality-control pathways shape tumor heterogeneity, immune evasion, and treatment outcomes across tumor, immune, and stromal compartments. In breast cancer, subtype-specific mitochondrial programs influence oxidative phosphorylation, fatty acid oxidation, glutaminolysis, lactate accumulation, and mtDAMP signaling, thereby contributing to immune suppression and therapeutic resistance. We further discuss how mitochondrial regulation of apoptosis, ferroptosis, cuproptosis, and pyroptosis reveals both therapeutic opportunities and unresolved limitations. Although mitochondria-targeted strategies show translational promise, their clinical application remains constrained by metabolic heterogeneity, adaptive rewiring, immune-cell liability, and insufficient biomarkers. Overall, mitochondria represent a context-dependent therapeutic axis in breast cancer.

Protein turnover and extracellular proteolysis continuously generate diverse peptide fragments within biological systems, yet the metabolic and pharmacological implications of these peptides remain incompletely understood. Among these transporters, members of the solute carrier family 15 (SLC15), including peptide transporter 1 (PEPT1/SLC15A1) and peptide transporter 2 (PEPT2/SLC15A2), mediate the proton-coupled uptake of dipeptides, tripeptides, and structurally related compounds across cellular membranes. While these transporters have been extensively studied in the context of intestinal peptide absorption and drug delivery, their potential roles in cancer biology remain incompletely understood. Tumor microenvironments are characterized by extensive proteolysis and dynamic metabolic remodeling, processes that can generate diverse peptide fragments derived from extracellular matrix proteins and intracellular protein turnover. These peptides may accumulate locally and potentially serve as substrates for cellular peptide transport systems. Once internalized through peptide transporters, dipeptides are typically hydrolyzed into free amino acids that can support biosynthetic pathways, energy metabolism, and cellular growth. In addition to their potential metabolic roles, certain endogenous dipeptides have also been reported to influence cellular signaling pathways and redox homeostasis. The broad substrate specificity of peptide transporters has also attracted significant interest in pharmacology because numerous clinically used drugs exploit these transport systems for efficient cellular uptake. This property raises the possibility that peptide transporters may be utilized for transporter-mediated drug delivery strategies, including the development of peptide-modified prodrugs or dipeptide–drug conjugates. In this review, we summarize the molecular characteristics and physiological functions of dipeptide transport systems with a particular focus on the SLC15 transporter family. We then discuss emerging evidence linking peptide transporters to tumor metabolism and the tumor microenvironment. Finally, we highlight current progress and future perspectives in exploiting peptide transport systems for transporter-mediated drug delivery and therapeutic targeting in cancer.

Background Dysregulated microRNAs (miRNAs) are critical contributors to breast cancer biology, yet the functional roles of many remain incompletely understood. miR-99b-5p has been widely characterized as a tumor-suppressive miRNA in numerous cancer types, where its expression is consistently reduced in tumors compared with normal tissues. In contrast, our analyses of breast cancer datasets revealed a unique expression pattern: miR-99b-5p is significantly upregulated in breast tumors, suggesting a context-dependent oncogenic function. In this study, we identified miR-99b-5p as an oncogenic driver in triple-negative breast cancer (TNBC). Methods and results TCGA-based expression profiling confirmed its elevated levels in breast tumors. Functional assays demonstrated that downregulation of miR-99b-5p in TNBC cells inhibits proliferation and induces apoptosis, indicating a critical role in sustaining tumor cell survival. To elucidate the molecular mechanisms underlying this activity, we performed AGO2-RNA immunoprecipitation followed by high-throughput sequencing (AGO2-RIP-Seq), enabling unbiased identification of miR-99b-5p-associated transcripts. Pathway enrichment analyses revealed that its direct targets converge on apoptotic regulation, cell-cycle control, and ubiquitin-mediated protein degradation. Mechanistic validation through qRT-PCR, Western blotting, and luciferase assays confirmed that miR-99b-5p modulates the TRAIL-R signaling pathway via DR5 and BAK, attenuating apoptotic signaling. In vivo studies using xenograft models established with MDA-MB-231 cells stably expressing miR-99b-5p knockdown showed marked tumor regression, further supporting its oncogenic role. Conclusion Collectively, these findings establish miR-99b-5p as a context-specific oncogenic miRNA in breast cancer and a promising therapeutic target, particularly for TNBC, where targeted treatment options remain limited.

Monotherapy cancer drug response prediction (DRP) models predict the response of a cell line to a given drug. Analyzing these models' performance includes assessing their ability to predict the response of cell lines to new drugs, i.e., drugs that are not in the training set. Drug-blind prediction displays greatly diminished performance or outright failure across a wide range of model architectures and different large pharmacogenomic datasets. Drug-blind failure is hypothesized to be caused by the relatively limited set of drugs present in these datasets. The time and cost associated with further cell line experiments is significant, and it is impossible to predict beforehand how much data would be enough to overcome drug-blind failure. We must first define how current data contributes to drug-blind failure before attempting to remedy drug-blind failure with further data collection. In this work, we quantify the extent to which drug-blind generalizability relies on mechanistic overlap of drugs between training and testing splits. We first identify that the majority of mixed set DRP model performance can be attributed to drug overfitting, likely inhibiting generalization and preventing accurate analysis. Then, by specifically probing the drug-blind ability of models, we reveal the sources of generalizable drug features are confined to shared mechanisms of action and related pathways. Furthermore, we observed that, for certain mechanisms, we can significantly improve performance by limiting the training of models to a single mechanism compared to training on all drugs simultaneously. Across multiple different model architectures examined in this paper, we observe that drug-blind performance is a poor benchmark for DRP as it does not describe model behavior, it describes dataset behavior. Our investigation displays that these deep learning models trained on large, monotherapy cell line panels can more accurately describe mechanism of action of drugs rather than their advertised connection to broader cancer biology.

Nanoparticles (NPs) are a promising tool for cancer therapy, yet few have successfully reached clinical application. Current nanomedicine development pipelines are focused on optimizing the physical properties of NPs, overlooking the impact of cancer biology on their behavior. Here, we show that the polyethyleneimine-functionalized, silica-coated gold NPs (Au@mSi-PEI) exhibit distinct accumulation and penetration patterns in 3D spheroids derived from four spheroid models (representative of lung, colon, breast, and cervical cancer). We uncover an inverse relationship between NP uptake and penetration: spheroids with slower internalization show deeper NP diffusion. Proteomic analysis revealed that tumor-specific expression of endocytic and extracellular matrix proteins underlies this variability. Our findings challenge the prevailing 'one-size-fits-all' approach and highlight the need to integrate cancer biology into NP design. Tailoring NPs to the unique cellular and extracellular features of each tumor type will be critical for developing more effective and clinically relevant nanotherapies.

Microfluidics has revolutionized cancer research by transforming how we study, diagnose, and test treatments, providing valuable insights into disease mechanisms and therapeutic responses. Through miniaturization, automation, and parallelization, microfluidic devices have standardized analytical assays and enhanced the accuracy and reliability of diagnostic and screening procedures, attracting the interest of pharmaceutical industry, laboratories, and clinicians. The use of advanced biofabrication techniques and biomaterials has further enabled the creation of sophisticated microphysiological devices integrating biomimetic tissue-like structures, closely mimicking the cellular and structural complexity of the native tumor microenvironment. This advanced generation of microfluidic platforms surpass conventional approaches that rely on synthetic, rigid, and planar materials, providing a more realistic representation of cancer biology. Moreover, the incorporation of miniaturized biosensors enabling real-time, multiplex, and precise monitoring of biological processes and biomarker presence overcomes the limitations of traditional screening methods, generating high-resolution data that can directly inform clinical decision-making when translated into practice. Herein, we describe how the convergence of microfluidics, biofabrication, and biosensor technologies is shaping a new paradigm in cancer research, driving advancements in disease modeling, drug screening, and diagnosis. While challenges remain for widespread clinical adoption, this integrated approach holds immense potential to transform cancer management and improve patient outcome.

CRISPR-based tools have quickly moved from specialist techniques to routine instruments in biology and medicine, and they are now central to large-scale loss-of-function and perturbation screens. In this review, we focus on how pooled CRISPR screens are used to interrogate gene function in living cells, most often through cell fitness or simple selectable markers, and contrast this with arrayed formats that trade throughput for richer molecular readouts, such as transcriptome-wide changes. We bring together current strategies for library design, delivery, and selection and show how different Cas nucleases, including Cas9, Cas12, and Cas13, broaden the range of genome and transcriptome perturbations that can be assayed. We then discuss recent applications in drug response, viral infection, and cancer biology and consider how improvements in high-content technologies, data analysis, and emerging diagnostic uses are likely to shape the next generation of CRISPR-based screening studies.

Groups 8, 11, and 12 of the periodic table contain several biologically relevant trace elements, among which iron, copper, and zinc play critical roles in numerous cellular processes, including oxygen homeostasis, enzymatic activity, mitochondrial metabolism, reactive oxygen species (ROS) regulation, DNA synthesis, and gene expression. These elements are essential for maintaining cellular physiology; however, disturbances in their homeostasis can trigger a cascade of molecular events within the tissue microenvironment.This review highlights the interconnected regulatory pathways of iron, copper, and zinc and discusses their dual roles in cancer biology, functioning both as promoters of tumour progression and as mediators of tumour suppression. We further examine the mechanisms through which metal dysregulation contributes to cellular toxicity, oxidative stress, and metabolic reprogramming in cancer. In addition, emerging therapeutic strategies targeting metal homeostasis are discussed, including approaches aimed at modulating metal overload, deficiency, and metal-dependent signalling pathways.By integrating current knowledge on the biological roles and pathological consequences of trace metal imbalance, this review provides a comprehensive perspective on how metal dyshomeostasis contributes to cancer development and highlights the potential of metal-targeted therapeutic strategies in cancer management.

Invasive lobular carcinoma (ILC) is the second most common subtype of breast cancer after invasive breast cancer of no special type (IBC-NST). This retrospective analysis of the MINDACT trial investigated transcriptomic differences between estrogen receptor-positive/HER2-negative (ER+/HER2-) ILC versus ER+/HER2- IBC-NST, classic and non-classic ER+/HER2- ILC, and, recurring and non-recurring ER+/HER2- ILC in patients with a low genomic risk and either a low (cL/gL) or high clinical risk (cH/gL). We analyzed 4261 ER+/HER2- tumors (63.7%, 464 ILC, 3798 IBC-NST) with central pathology review. Differential gene expression analysis was adjusted for age and grade, followed by gene set enrichment analysis. Adjusted regression models evaluated associations of transcriptomic profiles with disease-free (DFS) and distant recurrence-free survival (DRFS). An increased expression of CDH1 (E-cadherin) in IBC-NST compared to ILC was observed. ILC showed more uptake of extracellular lipid sources (LPL, CD36, LEP, LEPR), while IBC-NST favored lipid synthesis (FASN). Decreased ER-signaling, increased PI3K/Akt-signaling, and differences related to the extracellular matrix was also observed in ILC. Classic and non-classic ILC differed subtly, notably in cell cycle regulation. In ER+/HER2- ILC patients with a cL/gL risk, enrichment of apoptosis, inflammatory response, hypoxia and oncogenic signaling (PI3K/Akt, Ras, c-Myc) was associated with worse survival. In contrast, in the cH/gL group, associations between ILC transcriptomic features and survival were more subtle. This represents the largest transcriptomic dataset for ILC from a clinical trial with central histology review. Findings may provide insights to refine treatment and relapse risk assessment for ILC patients.

Pediatric solid tumors remain among the most treatment-refractory childhood malignancies, defined by biological features that have largely resisted the immunotherapeutic advances transforming adult oncology. Exceptionally low tumor mutational burden, sparse neoantigen landscapes, and profoundly immunosuppressive tumor microenvironments collectively undermine the T cell-dependent mechanisms on which most current immunotherapies depend. Yet the field is undergoing a meaningful shift. Anti-GD2 monoclonal antibodies have established a survival benchmark in high-risk neuroblastoma, and next-generation antibody-drug conjugates and bispecific T cell engagers targeting GD2, B7-H3, and GPC2 are extending the reach of antibody-based approaches across pediatric histologies. CAR T cell therapies have demonstrated clinical feasibility against multiple targets, with advanced engineering strategies, including cytokine armoring, bispecific constructs, and locoregional delivery, beginning to address fundamental barriers such as poor tumor infiltration, limited persistence, and antigen escape. Immune checkpoint inhibitors, while largely ineffective as monotherapy in unselected populations, induce durable responses in molecularly defined subsets such as mismatch repair-deficient and hypermutated tumors. Emerging platforms, including oncolytic virotherapy, NK cell engagers, and neoantigen vaccines, offer rational strategies to convert immunologically cold tumors into treatment-responsive phenotypes. Together, these advances point toward a future of combination immunotherapy tailored to the distinct immune biology of childhood cancers.