Colorectal cancer (CRC) is the second most common cancer type that results in significant mortality, the primary cause of which is associated with metastasis. Epithelial-mesenchymal transition (EMT) is a biological process that converts polarized epithelial cells into migratory mesenchymal states, which is positively correlated with the dissemination of the tumor cells from the primary tumor site and is thus linked to metastasis. Mesenchymal markers are the proteins that are up-regulated upon initiation of EMT. This review aims to provide a comprehensive overview of the role of mesenchymal markers in CRC metastasis. Upon thorough data mining, fibronectin, vimentin, N-cadherin, and β-catenin were defined as the distinguished mesenchymal markers that are well-studied in the context of CRC metastasis. Expression of these markers was positively correlated with aggressive CRC stages. However, the underlying molecular mechanisms through which they facilitate CRC progression are partly explored. Fibronectin was reported to affect cell migration and invasion via NF-kB/p53 and ITGA5/FAK-P/RhoGTPase axis, while its Extra Domain A (EDA) regulates the lymphangiogenesis via VEGF-C/PI3K/AKT axis. For vimentin and N-cadherin, few upstream regulators have been reported; however, the downstream pathways via which they affect migration and invasion remain to be explored. β-catenin, a well explored molecule for CRC onset, has limited reports in relation to metastatic progression. Wnt/β-catenin signalling has been reported to promote migration and invasion in primary CRC, while it impedes the same in advanced CRC background. There are future scopes for mechanistic research on the underexplored mesenchymal markers, whereas the mechanistically explored molecules need to be tested clinically.

OBJECTIVE: Breast cancer is the most frequently diagnosed malignancy in women and a leading cause of cancer-related mortality. Conventional prognostic tools may not fully capture disease outcomes. MicroRNA (miR) expression has emerged as a potential prognostic factor, though findings remain inconsistent. This systematic review and meta-analysis assess the prognostic role of miR-190, miR-221, and miR-381 in predicting overall survival (OS) among breast cancer patients. MATERIALS AND METHODS: A comprehensive literature search in PubMed, Embase, and Scopus identified relevant studies. Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated to assess the relationship between miR expression and OS. Subgroup analyses were conducted to explore potential sources of heterogeneity. RESULTS: Four studies on miR-221, four on miR-190, and three on miR-381 met inclusion criteria. High miR-190 expression was significantly associated with improved OS (HR: 0.63; 95% CI: 0.47-0.84), as was miR-381 (HR: 0.64; 95% CI: 0.52-0.79). No significant association was found between miR-221 expression and OS (HR: 1.12; 95% CI: 0.86-1.46). Subgroup analysis reinforced these findings, and Newcastle-Ottawa scale assessment indicated low publication bias in 10 out of 11. CONCLUSIONS: Elevated miR-190 and miR-381 levels are associated with improved OS in breast cancer, whereas the prognostic role of miR-221 remains unclear. These findings underscore the potential of miR-190 and miR-381 as prognostic biomarkers.

Akt (v-akt murine thymoma virus oncogene homologue) is a well-known serine-threonine kinase that functions as a central node in various important signal cascades involved in cellular maintenance. Akt has also been implicated in oncogenic malignancies as evidenced by protein overexpression, activation and somatic aberration of components in the phosphoinositide-3 kinase-Akt pathway. As such, Akt is a potential target in cancer therapy. Akt is frequently activated in human cancer tissues not only due to aberrant upstream signaling, but also by genetic mutations in AKT itself. This leads to the aberrant activation of pathways downstream of Akt that regulate cell-cycle progression and metabolism as well as activation of transcription factors that promote oncogenesis. In this review, we summarize previous research on Akt, including the molecular mechanisms underlying Akt signal transduction, as well as its physiologic roles and the pathologic consequences when dysregulated. We also discuss the roles of dysregulated protein overexpression/activation, increases in gene copy number, single nucleotide polymorphisms and the network of non-coding RNAs that regulate this pathway, with a particular focus on lung carcinomas. Finally, we discuss strategies that might lead to more effective targeting of Akt for clinical cancer therapy.

Inhibitors of DNA-binding (Id) proteins constitute a family of repressor factors that modulate a multitude of cellular processes and have been linked to tumor aggressiveness, resistance to chemotherapy, angiogenesis, and worse prognosis in numerous malignancies. This review explores the role of Id proteins in the pathogenesis of neuroendocrine neoplasms (NENs). The findings revealed that this family of proteins shows significant overexpression in tumors such as small cell lung carcinoma (SCLC), neuroendocrine prostate carcinoma (NEPC), and medullary thyroid carcinoma (MTC), although the role of epigenetics in regulating Id proteins within NENs remains poorly understood, with most evidence limited to NEPC. These results underscore the potential of Id proteins not only as diagnostic biomarkers and promising therapeutic targets for the management of NENs, but also highlight the need for further research to better understand their epigenetic regulation and broader role in these tumors.

Lymphoma is a common malignancy characterized by diverse pathological types and marked heterogeneity. Distinct subtypes of lymphomas are markedly different in their clinical manifestations, treatment approaches and prognostic outcomes. With the rapid development of molecular biology techniques, antitumor research has stepped into an era of precision medicine. Biomarkers, with high sensitivity and specificity, are expected to function in early diagnosis, targeted treatment and prognostic estimation for cancer and enhance the survival rate and life quality of patients. In this regard, proteomics technology, with the capability to systematically identify and quantify the dynamic protein alterations in tissues or cells, thereby facilitating the discovery of novel tumor potential candidates, has attracted significant scientific attention. The present article aimed to review most up‑to‑date research progress of lymphoma‑related biomarkers discovered based on proteomics technology, focusing on the potential application of these markers in the diagnosis, therapy and prognosis of each lymphoma subtype, and discuss the role proteomics may serve in future development of lymphoma research and clinical practice.

Brain tumors are one of the most severe types of malignant tumors and glioma accounts for ~80% of malignant brain tumors. The current treatment methods for glioma are limited and patients with glioma often experience relapse following treatment, which leads to a poor prognosis for these patients. Therefore, novel therapeutic targets and methods urgently need to be explored. The present review screened studies that mainly focused on the epigenetic regulation of small guanosine triphosphate (GTP)ase in glioma. These small GTPases participate in most cellular biological processes, including differentiation, proliferation, cell migration, apoptosis, vesicle and organelle dynamics and transport, nuclear dynamics and cytoskeleton regulation. Due to the diversity and importance of the biological functions of small GTPases, an increasing number of studies have focused on them; however, the incidence of changes in the gene structure of small GTPases is considered to be low in glioma. Several studies have shown that the abnormal expression of genes encoding small GTPases is often influenced by epigenetic regulation in glioma. Epigenetic regulation is a dynamic and reversible process, which implies that the reversal of abnormal epigenetic modifications is a potential treatment strategy for glioma. These previous studies, which are summarized in the present review, not only provide new therapeutic targets and prognostic markers, but also provide information regarding the treatment of glioma. The current review may provide valuable insights for future research and promote the clinical translation of relevant research results.

Similar to many other cancer types, liver malignancies pose the common challenges of late detection of primary tumors and recurrences. Liquid biopsies, which assess the presence of circulating tumor DNA, have emerged as a novel, non-invasive clinical tool for diagnostic and surveillance purposes. This review represents an introductory and comprehensive overview of the current circulating tumor DNA (ctDNA) literature relevant to primary and secondary liver malignancies. Herein, we highlight key findings, landmark discoveries, challenges, and future directions.

Maintaining genomic stability is essential for reducing the risk of carcinogenesis. Homologous recombination (HR) is a high‑fidelity DNA repair mechanism that addresses double‑strand breaks and interstrand crosslinks. The present review examined two key components of HR: RAD51, the eukaryotic recombinase and PALB2, a scaffolding protein. Their structural and functional roles are explored in the context of breast and ovarian cancer. RAD51 facilitates homology search and strand invasion, while PALB2 links BRCA1 and BRCA2, stabilizing RAD51 filaments. Mutations in these genes compromise HR, increasing susceptibility to various cancers and impacting treatment efficacy by impairing DNA repair. The present review discussed the clinical implications of RAD51 and PALB2 mutations, focusing on risk stratification, PARP inhibitor efficacy and emerging therapies. Additionally, it highlighted the potential of RAD51 and PALB2 as biomarkers and therapeutic targets, contributing to advances in personalized cancer management.

Cervical cancer (CC) is the fourth commonest malignant tumor among women worldwide and is characterized by high heterogeneity and a complex ecosystem. A comprehensive understanding of the heterogeneity of tumors and the tumor microenvironment (TME) is crucial for effective CC management. Single-cell RNA sequencing (scRNA-seq) is a powerful tool that can be employed to unveil the heterogeneity of tumors and the TME, as well as to elucidate the evolutionary trajectories of tumors. Spatial transcriptomics (ST) technology, on the other hand, can address the complexity and diversity of the spatial microenvironment of tumors, thereby compensating for the limitations of scRNA-seq. As emerging technologies, both scRNA-seq and ST are increasingly being utilized in CC research. In this review, we summarized the latest advancements in scRNA-seq and ST for CC, with a focus on investigating tumor heterogeneity, the TME, tumor evolutionary trajectories, treatment resistance mechanisms, and potential therapeutic targets. These insights collectively contribute to the development of more effective treatment and prevention strategies for CC.

Lynch syndrome (LS), also known as hereditary non-polyposis colorectal cancer (HNPCC), is an inherited condition associated with a higher risk of colorectal cancer (CRC) and other cancers. It is caused by germline mutations in DNA mismatch repair (MMR) genes, including MLH1, MSH2, MSH6 and PMS2. These mutations lead to microsatellite instability (MSI) and defective DNA repair mechanisms, resulting in increased cancer risk. Early detection of LS is crucial for effective management and cancer prevention. Endoscopic surveillance, particularly regular colonoscopy, is recommended for individuals with LS to detect CRC at early stages. Additionally, universal screening of CRC for MMR deficiency can help identify at-risk individuals. Genetic counseling plays a valuable role in LS by guiding patients and their families in understanding the genetic basis, making informed decisions regarding surveillance and prevention, and offering reproductive options to reduce the transmission of pathogenic variants of the offspring. The aim of this review is to outline current strategies for the diagnosis, surveillance, and management of LS, with a focus on the role of genetic counseling, endoscopic screening, and emerging therapeutic approaches to mitigate cancer risk in affected individuals.

In recent years, the development of targeted therapies for tumors with KRAS mutations has progressed rapidly, rendering the notion of KRAS as "undruggable" outdated. However, targeted therapies for KRAS mutations still face numerous challenges, including resistance, efficacy concerns, toxicity issues, and hurdles in drug development. Exploring alternative treatment modalities is thus essential. Extensive research has demonstrated that KRAS mutations significantly influence the immune microenvironment, presenting both challenges and opportunities for immunotherapy. Interestingly, it has been observed that different KRAS mutations and co-mutation subtypes exhibit significant variations in their immunological microenvironments, which undoubtedly impact immunotherapy choices. Here, we review the history of KRAS-targeted therapy, highlighting existing challenges, and summarize changes in the immune microenvironment of KRAS-mutated cancers and their potential therapeutic targets. We compare differences in the immune microenvironment across various mutation types and co-mutation subtypes, and offer perspectives on future research directions.

Chimeric antigen receptor T (CAR-T) cell therapies have transformed the treatment of relapsed/refractory (R/R) B-cell malignancies and multiple myeloma by redirecting activated T cells to CD19- or BCMA-expressing tumor cells. However, this approach has yet to be approved for acute myeloid leukemia (AML), the most common acute leukemia in adults and the elderly. Simultaneously, CAR-T cell therapies continue to face significant challenges in the treatment of solid tumors. The primary challenge in developing CAR-T cell therapies for AML is the absence of an ideal target antigen that is both effective and safe, as AML cells share most surface antigens with healthy hematopoietic stem and progenitor cells (HSPCs). Simultaneously targeting antigen expression on both AML cells and HSPCs may result in life-threatening on-target/off-tumor toxicities such as prolonged myeloablation. In addition, the immunosuppressive nature of the AML tumor microenvironment has a detrimental effect on the immune response. This review begins with a comprehensive overview of CAR-T cell therapy for cancer, covering the structure of CAR-T cells and the history of their clinical application. It then explores the current landscape of CAR-T cell therapy in both hematologic malignancies and solid tumors. Finally, the review delves into the specific challenges of applying CAR-T cell therapy to AML, highlights ongoing global clinical trials, and outlines potential future directions for developing effective CAR-T cell-based treatments for relapsed/refractory AML.

Telomere biology still remains a topic of interest in life sciences. Analysis of several thousand clinical samples from healthy individuals performed in recent years has shown that the telomere length (TL) in peripheral blood leukocytes correlates with the TL in cells of internal organ and reflects their condition. TL decreases under the influence of damaging factors and can serve as an indicator of health status. The telomere shortening leads to the cell proliferation arrest and is considered as a marker of replicative aging of proliferating cells. A decrease in the TL in peripheral blood leukocytes is viewed as an indicator of organism aging. Recent studies have allowed to formulate the concept on the role of the CST-polymerase α/primase in the C-strand fill in after completion of 3'G overhang synthesis by telomerase during telomere replication. The discovery of the telomeric RNA (TERRA) and its role in the regulation of telomerase activity (TA) and alternative lengthening of telomeres, as well as the possibility of TERRA translation, has provided evidence of the complex epigenetic regulation of the TL maintenance. Analysis of the published data indicates that telomeres are dynamic structures, whose length undergoes significant changes under the influence of damaging factors. TL is determined not only by the chronological age, but also by the exposure to the exogenous and endogenous deleterious factors during the lifetime. A decrease in the TL due to inherited mutations in the genes coding for proteins involved in the telomere structure formation and telomere replication (primarily, proteins of the shelterin and CST complexes and telomerase) has been found in a number of hereditary diseases - telomeropathies. The assessment of TL and TA is of great importance for the diagnostics of telomeropathies and can be useful in the diagnostics of cancer. Analysis of TL can be used for monitoring the health status (e.g., in the case of exposure to ionizing radiation and space flight factors), as well as predicting individual's sensitivity to the action of various damaging agents. The application of modern advancement in genetic technologies in the analysis of TL and TA makes it available for the use in clinical and epidemiological studies, diagnostics of telomeropathies, and monitoring of astronauts' health.

Bladder cancer (BCa) remains a significant clinical challenge because of high recurrence rates and variable response to immunotherapy and chemotherapy. Recent studies have highlighted the role of N6-methyladenosine (m6A) modification in RNA in the regulation of various cellular processes, including tumor progression and drug resistance. The review examines the impact of m6A methylation on BCa pathogenesis, with a particular special focus on the role of m6A pathway factors and m6A-modified RNAs in tumorigenesis, proliferation, invasion, and migration of cancer cells. The mechanisms of m6A-mediated chemotherapy resistance in BCa cells are discussed, including single nucleotide polymorphisms in m6A-associated patterns. Significant advances in the high-throughput analysis of m6A methylation have enabled development of novel m6A-based biomarkers for the risk assessment, early diagnostics, and prediction of relapse and treatment response in BCa. The review outlines the prospects of the m6A-based molecular diagnostics in BCa.

RNA G-quadruplexes (rG4s) are non-canonical, four-stranded secondary structures formed by guanine-rich RNA sequences. These dynamic elements have garnered significant attention for their critical roles in regulating gene expression, including translation, alternative splicing, mRNA localization, and stability. This review synthesizes recent progress in understanding the structural determinants and formation dynamics of rG4s, highlighting the contributions of sequence motifs, ionic conditions, and RNA-binding proteins to their stability and function. Functional studies reveal that rG4s modulate key oncogenic transcripts (e.g., MYC, BCL2), contribute to splicing regulation, and influence intracellular RNA trafficking. In pathological contexts, rG4s have been implicated in the molecular etiology of cancers, neurodegenerative diseases such as amyotrophic lateral sclerosis and Fragile X syndrome, and viral replication mechanisms in pathogens including HIV and SARS-CoV-2. Advances in high-throughput techniques, such as G4-seq, rG4-seq, and live-cell imaging, have facilitated the global identification and characterization of rG4s in physiological and disease settings. Moreover, the therapeutic targeting of rG4s using small molecules holds promise for selective gene regulation and biomarker development. Comparative analyses across in vitro, in vivo, and clinical studies underscore the cell-type-specific and context-dependent roles of rG4s, especially in mediating stress responses and apoptosis. Despite methodological limitations and challenges in achieving targeted delivery, rG4s represent a compelling frontier for precision medicine. This review outlines current insights and future directions toward harnessing rG4 biology for therapeutic innovation.

Prostate cancer (PC) is a leading cause of male cancer mortality, with bone metastasis (BM) being a frequent and debilitating complication. Despite therapeutic advancements, the molecular mechanisms underlying BM remain poorly understood. This study aims to bridge this gap by integrating bibliometric analysis with bioinformatics to provide a comprehensive overview of the academic trends and molecular profiles associated with prostate cancer bone metastasis (PCBM).

Colorectal cancer (CRC) is the third highest malignant tumor in the world in terms of incidence rate, accounting for about 10% of all cancer cases and the second leading cause of cancer related deaths. Timely diagnosis and effective treatment are key to significantly improving the survival rate of CRC patients. Various factors including gender, environmental factors, lifestyle choices, and genetic predisposition are all causes of the onset of CRC. Circular RNA(circRNA) mainly exists in cancer cells and tissues, solid tumors, peripheral blood, exosomes, and body fluids (such as serum, plasma, and saliva). Due to their resistance to degradation and presence in body fluids, CircRNA is non-invasive and an ideal candidate for liquid biopsy, thus having high diagnostic potential. Current research has found that circRNA can regulate the proliferation, migration, invasion, and apoptosis of CRC cells.

Neoantigens are tumor-specific antigens presented exclusively by cancer cells. These antigens are recognized as nonself by the host immune system, thereby eliciting an antitumor T-cell response. This response is significantly enhanced through neoantigen-based immunotherapies, such as personalized cancer vaccines. The repertoire of neoantigens is unique to each cancer patient, necessitating neoantigen prediction for designing patient-specific immunotherapies. This review presents the computational methods and data resources used for neoantigen prediction, as well as the prediction-associated challenges. Neoantigen prediction typically uses human leukocyte antigen typing, RNA-seq transcript quantification, somatic variant calling, peptide-major histocompatibility complex (pMHC) presentation prediction, and pMHC recognition prediction as the main computational steps. The immunoinformatics tools used for these steps and for the overall prediction of neoantigens are systematically summarized and detailed in this review.

DNA methylation in breast tumours has been extensively studied and has provided valuable insights into the clinical heterogeneity of breast cancer. In this review, we summarise the current literature that has used DNA methylation markers to subtype breast cancer and predict progression and survival. Widespread methylation differences have been observed across breast cancer subtypes at both the candidate genes and in genome-wide analyses, most notably between oestrogen receptor (ER) positive and ER-negative subtypes and for triple-negative tumours. Studies that attempted to create breast cancer subtypes using methylation data showed limited agreement in their capacity to group breast tumours, possibly due to methodological differences. Although many studies have reported associations of tumour DNA methylation with breast cancer outcomes and used machine learning methods to derive prediction models for survival, the extent to which these would replicate in independent datasets is currently unclear. We conclude that despite the potential of genome-wide methylation markers to unravel the heterogeneity of breast cancer, they currently appear to have limited clinical utility. Larger studies and replication of findings across studies are required to address the limitations of the existing literature.

Drug resistance poses a significant challenge in cancer therapy, contributing to rapid recurrence, disease progression, and high patient mortality. Despite its critical impact, few reliable predictors for cancer drug response or failure have been established for clinical application. Tumor heterogeneity and the tumor microenvironment (TME) are pivotal factors influencing cancer drug efficacy and resistance. Tumor heterogeneity leads to variable therapeutic responses among patients, while dynamic interactions between cancer cells and the TME enhance tumor survival and proliferation, underscoring the urgent need to identify cellular hallmarks for predicting drug response and resistance. Single-cell and spatial omics technologies provide high-resolution insights into gene expression at the individual cell level, capturing intercellular heterogeneity and revealing the underlying pathologies, mechanisms, and cellular interactions. This review delves into the principles, methodologies, and workflows of single-cell and spatial omics in cancer drug research, highlighting key hallmarks involving tumor heterogeneity, TME reprogramming, cell-cell interactions, metabolic modulation, and signaling pathway regulation in drug treatment at single-cell and spatial levels. Furthermore, we synthesize predictive cellular biomarkers for cancer drug response and resistance across 25 cancer types, paving the way for advancements in cancer precision medicine.