Background: Double-strand breaks (DSBs) are universally acknowledged as the most detrimental type of DNA damage, and their effective repair primarily depends on the non-homologous end joining (NHEJ) pathway. Such DSBs, which require NHEJ for resolution, can arise from intrinsic and extrinsic DNA-damaging factors or emerge naturally during essential biological processes like V(D)J recombination and antibody class switch recombination.

Main Body: Failure to properly repair DSBs may lead to genomic instability, disruption of cellular functions, and immunodeficiency, thereby promoting the development of hematologic malignancies. Conversely, overexpression of NHEJ-related genes can enhance resistance to DNA-damaging therapies in these cancers. Analyzing mutations in key classical NHEJ (cNHEJ) components and understanding their mechanisms could provide valuable biomarkers for predicting therapeutic outcomes and guiding treatment decisions. Consequently, defects in cNHEJ may offer insights into the development of novel drugs targeting DNA repair pathways.

Conclusion: We focus on genetic changes and alterations in gene regulation, while also providing an overview of cNHEJ.

Recent high-throughput sequencing technologies have discovered various polymerase II transcribed transcripts. The majority of them are non-protein-coding, understudied and poorly conserved. Non-coding transcripts are categorised based on their location in the genome and the direction in which they are transcribed; these categories classify a non-coding transcript as either antisense, intergenic or divergent. The RNAs belonging to divergent classes consist of two transcripts, transcribed in sense and antisense direction, generated from the same promoter or locus. Multiple environmental and genetic cues can determine the regulation of these transcripts. One of the well-known signalling molecules, estrogen, has been shown to play a vital role in the activation and regulation of divergent transcripts by mediating effects through the estrogen receptors. Emerging studies have shown a strong causative effect between estrogen-regulated divergent transcripts and diseases such as cancer. However, few, viz., lncRNA67, CUPID1 and CUPID2, show a causal relationship with estrogen-dependent biology. This mini-review summarises their role in estrogen-dependent processes that may drive the research to identify novel estrogen-signalling regulators.

Cancer-associated fibroblasts (CAFs) represent critical cellular components of the tumor microenvironment and have garnered widespread attention in the field of tumor immunology. However, given the pronounced heterogeneity of CAFs, research investigating their impact on tumor immunity has yielded diverse and often contradictory results. Therefore, in this review, we have systematically summarized previous studies to comprehensively elucidate the role of CAFs in the tumor immune microenvironment and have explored the bidirectional regulatory effects of CAFs on immune cells and immune molecules within this complex niche. We highlight the multifaceted role of CAFs in cancer immunotherapy, focusing on their impact on immunotherapeutic efficacy, as well as the synergistic effects between CAF-targeted therapies and immunotherapies in anti-cancer treatment. Addressing the heterogeneity of CAFs, we also critically analyze controversies surrounding these cells in the field of tumor immunology and propose strategic directions for future investigations targeting this cell population. Our comprehensive analysis provides a strategic framework for future research directions and clinical translation of CAF-targeted strategies, ultimately facilitating the development of more effective and personalized cancer immunotherapeutic approaches.

Background: Viral hepatitis, particularly hepatitis B virus (HBV) and hepatitis C virus (HCV) infections, represent the predominant etiological factors for hepatocellular carcinoma (HCC) worldwide. HBV and HCV drive hepatocellular malignant transformation through complex molecular mechanisms that are both distinct and overlapping. Comprehensive elucidation of these mechanisms, particularly the role of viral-mediated remodeling of the tumor microenvironment, is crucial for developing novel preventive and diagnostic strategies as well as personalized therapeutic approaches.

Aim: This review aims to systematically elucidate the key molecular mechanisms underlying HBV- and HCV-related HCC development and progression (including virus-specific pathways and common pathways), to explore the translational potential of these mechanisms in clinical medicine, and to provide perspectives on future research frontiers.

Results: This review systematically elucidates the pathogenic mechanisms of HBV- and HCV-related HCC and provides comprehensive analysis of the common molecular mechanisms underlying viral hepatitis-to-HCC transformation. For HBV-related HCC, we focus on analyzing the following oncogenic mechanisms: genomic instability caused by HBV DNA integration, oncogenic effects of HBV proteins, and the impact of virus infection-mediated tumor microenvironment remodeling on immune responses. For HCV-related HCC, we focus on exploring the following oncogenic mechanisms: oncogenic mechanisms of viral proteins, virus infection-mediated metabolic disorders, functional dysregulation of immune cells in the microenvironment, and virus-induced hepatic fibrosis. Furthermore, we thoroughly investigated the common mechanisms underlying viral hepatitis-to-HCC transformation, including the construction of pro-inflammatory factor networks in chronic inflammatory microenvironments, virus-induced epigenetic alterations, and genomic instability. Based on current research, we further discuss future research directions and perspectives in this field.

Conclusion: This review systematically elucidates the pathogenic mechanisms of HBV- and HCV-related HCC and provides comprehensive analysis of the common molecular mechanisms underlying viral hepatitis-to-HCC transformation, with particular emphasis on the remodeling effects of viral infection on the HCC microenvironment, which hold significant clinical implications for developing novel preventive strategies, diagnostic biomarkers, and personalized therapeutic approaches. Through systematic analysis of the long-term effects of virus infection-induced epigenetic reprogramming in HCC development and progression, combined with multi-omics data to construct HCC risk prediction models, our findings provide scientific evidence for the development of early screening and precision treatment strategies. Meanwhile, investigating the relationship between viral integration patterns and HCC prognosis, and developing novel molecular classification methods, will facilitate the design of more individualized and precise treatment regimens for patients. Additionally, utilizing cutting-edge artificial intelligence technologies and developing innovative research approaches such as viral hepatitis-related liver organoid models will also provide novel insights and methodologies for reducing the incidence and mortality of viral hepatitis-related HCC.

Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of mortality and morbidity worldwide despite advancements in therapeutic options for the management of atherosclerosis (AS). Treatments that lower low-density lipoprotein (LDL) cholesterol levels, such as statins or proprotein convertase subtilisin/kexin type 9 inhibitors, have effectively reduced ASCVD risk. However, residual CVD risk remains high, highlighting the need for additional effective therapies. Recently, colchicine has been approved for managing AS, introducing new avenues for targeting inflammation, a key process in AS.

Various factors contribute to AS progression, such as endothelial dysfunction, leukocyte transmigration, vascular smooth muscle cell migration and phenotype-switching, increased lipid retention, production of pro-inflammatory cytokines and regulated cell death processes such as apoptosis. The annexin A (AnxA) family of proteins is well-known for their ability to bind Ca²⁺ and phospholipids, and they play diverse roles in inflammation, cell proliferation, migration, differentiation and signalling. Several AnxA proteins have been implicated in essential processes involved in AS development, including endothelial dysfunction, leukocyte transmigration and apoptosis.

In this mini-review, we highlight the roles of AnxA1, AnxA2, AnxA5, AnxA6, AnxA7 and AnxA8 in AS development and progression and their therapeutic potential in AS management.

Background: The intricate relationship between cellular ageing processes and cancer development represents one of the most significant challenges in contemporary oncology. As populations worldwide experience unprecedented demographic shifts towards advanced age, understanding the molecular mechanisms that link ageing to cancer initiation, progression, and therapeutic response has become essential for developing effective precision medicine approaches.

Main body: This review examines the fundamental molecular pathways through which ageing influences cancer biology, including telomere dysfunction, cellular senescence, DNA damage accumulation, and epigenetic alterations. These age-related changes create a permissive environment for oncogenesis while simultaneously affecting therapeutic efficacy and treatment tolerance. Key ageing-associated molecular signatures include p16^INK4a^ upregulation, shortened telomeres, increased DNA damage response activation, and altered chromatin structure. The accumulation of senescent cells with age contributes to chronic inflammation and tissue dysfunction that promotes tumour development. Additionally, age-related changes in drug metabolism, DNA repair capacity, and immune function significantly impact therapeutic outcomes. Recent advances in molecular ageing biomarkers, including transcriptomic ageing clocks and protein-based signatures, offer promising approaches for personalizing cancer treatment strategies. The integration of ageing biology into precision oncology frameworks presents opportunities for developing age-informed therapeutic protocols that optimize efficacy while minimizing toxicity. Emerging technologies, including artificial intelligence-driven molecular analysis and advanced imaging techniques, enable more precise characterization of ageing-cancer interactions at the cellular and tissue levels.

Conclusion: The molecular mechanisms underlying ageing-cancer relationships provide critical insights for advancing precision oncology approaches. Understanding these pathways enables the development of targeted interventions that account for age-related biological changes, ultimately improving therapeutic outcomes for older cancer patients. Future research must focus on translating molecular ageing discoveries into clinically actionable tools that enhance treatment personalization and optimize care delivery across the cancer continuum.