Editorial: Exploring molecular mechanisms in cancer through tumor molecular pathology

Tumor molecular pathology has become an indispensable discipline for understanding cancer initiation, progression, therapeutic response, and clinical heterogeneity (1). By integrating histopathological assessment with genomic, transcriptomic, proteomic, immunological, and functional analyses, this field bridges morphological diagnosis with molecularly informed clinical decision-making (1,2). As cancer treatment increasingly shifts toward precision oncology, molecular pathology provides the conceptual and technical foundation for identifying actionable alterations, refining prognostic stratification, guiding targeted therapy and immunotherapy, and uncovering novel mechanisms of tumor evolution and treatment resistance (1,3,4). This Research Topic, "Exploring Molecular Mechanisms in Cancer through Tumor Molecular Pathology," was established to provide a comprehensive platform for studies that investigate the molecular basis of tumor behavior and translate these insights into diagnostic, prognostic, and therapeutic advances. The collection brings together 19 articles, including 3 reviews, 12 original research articles, 2 case reports, 1 brief research report, and 1 technology and code article. Together, these contributions highlight the breadth of tumor molecular pathology, spanning cancerassociated viral oncogenesis, molecular diagnostics, rare genomic alterations, immune profiling, cell signaling, apoptosis regulation, therapeutic resistance, and biomarker-driven precision treatment.Several articles in this collection focus on molecular mechanisms that drive tumor development and progression. Xie et al. reviewed Epstein-Barr virus-driven molecular pathogenesis in primary pulmonary lymphoepithelial carcinoma, emphasizing the links among viral infection, tumor immune microenvironment, clinicopathological features, and potential EBV-targeted or immunotherapeutic strategies. Samaha et al. summarized the molecular pathogenesis of adult Tcell leukemia/lymphoma, highlighting the contributions of HTLV-1 infection, viral oncogenes, immune escape, and recurrent alterations in TCR/NF-κB, JAK/STAT, and apoptotic pathways. Sun et al. reviewed the Hippo signaling pathway in cervical cancer, particularly the crosstalk between HPV oncoproteins and YAP/TAZ-mediated transcriptional programs, and discussed its therapeutic potential. These reviews collectively provide conceptual frameworks for understanding how viral factors, signaling networks, and tumor-specific molecular dependencies shape malignant phenotypes.A group of original studies further expands the mechanistic landscape of cancer molecular pathology. Chen et al. demonstrated that ZC3H18 regulates alternative splicing events and cancerassociated pathways in cervical cancer, suggesting that RNA-binding proteins and splicing regulation may represent important therapeutic vulnerabilities. Chen et al. identified NOP56 as an oncogenic nucleolar protein in hepatocellular carcinoma that interacts with fibrillarin and activates the PI3K/AKT/CREB pathway to inhibit apoptosis. Yan et al. showed that endoplasmic reticulum stress-induced CLGN promotes apoptosis resistance in hepatocellular carcinoma through NF-κB signaling, while paeonol synergistically enhances antitumor efficacy by dual inhibition of CLGN and NF-κB. Lu et al. reported that CMSP suppresses oral squamous cell carcinoma progression by targeting the JAK2/STAT3/c-Myc axis. Chen et al. provided experimental evidence that HOXB7 drives bladder cancer progression through H-Ras/Raf-1/MEK/ERK signaling. These studies underscore the importance of pathway-level molecular pathology in identifying functional drivers and candidate therapeutic targets.Another major theme is the clinical application of molecular diagnostics and biomarker discovery. Mohamed et al. showed that combined PRSS22 and CEA mRNA analysis in lymph nodes can identify the majority of colon cancer patients who relapse within 12 years, supporting PRSS22 as a promising prognostic biomarker and potential therapeutic target. Zhang et al. found that TP53 and KRAS co-mutations are associated with worse outcomes in mucinous ovarian carcinoma, suggesting that tumor molecular profiling may improve prognostic assessment even in early- Collectively, the studies in this Research Topic highlight the expanding role of tumor molecular pathology in bridging molecular mechanisms with translational and clinical oncology. By integrating molecular profiling, functional validation, biomarker discovery, computational analysis, and therapeutic exploration, these works provide deeper insights into tumor heterogeneity, immune regulation, signaling pathways, and therapy resistance across multiple cancer types. Importantly, this collection reflects emerging trends in cancer research, including multi-omics integration, AI-assisted molecular diagnostics, structure-guided precision medicine, and personalized therapeutic strategies. Beyond advancing mechanistic understanding, these studies also emphasize the growing importance of translating molecular discoveries into clinically actionable applications. We anticipate that the findings presented here will promote interdisciplinary collaboration and contribute to the development of more accurate diagnostic tools, more effective targeted therapies, and more individualized treatment paradigms in precision oncology.