Metabolic reprogramming is a hallmark of cancer, with the Warburg effect-driven aerobic glycolysis leading to a substantial accumulation of lactate in the tumor microenvironment. For a long time, lactate was considered a mere metabolic end product; however, recent studies have found that it acts as an important signaling molecule, profoundly influencing tumor progression by inducing a novel post-translational modification - lactylation. Lactylation, driven by lactate, occurs on both histones and non-histone proteins and is finely regulated by the 'writer' 'eraser' and 'reader' mechanisms, thereby altering the function of target proteins and gene expression. This review systematically explores the bidirectional regulatory network between glycolytic reprogramming and lactylation: on one hand, key glycolytic regulators promote lactate production, thereby increasing lactylation levels; on the other hand, lactylation can feedback to regulate the activity and expression of key glycolytic enzymes, forming a pro-tumor positive feedback loop. This interaction plays a central role in tumor proliferation, metastasis, DNA damage repair, and immune evasion. Consequently, targeting lactate production, lactate transport, or the lactylation process itself has emerged as a highly promising anti-cancer strategy and shows potential synergy with existing therapies such as immune checkpoint inhibitors. In-depth analysis of the glycolysis-lactylation axis will provide a crucial theoretical basis for developing novel cancer treatment approaches.
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Global cancer statistics in 2022 ranked lung cancer as the leading cause of cancer incidence and mortality worldwide, with lymph node metastasis serving as a pivotal determinant of prognosis and treatment strategy. Extranodal extension (ENE) refers to the pathological phenomenon where tumor cells breach the lymph node capsule and invade surrounding tissues. In non-small cell lung cancer (NSCLC), although ENE has not yet been formally incorporated into the tumor-node-metastasis (TNM) staging system, its clinical value is gaining increasing attention. This review systematically summarizes the current research progress regarding the definition, diagnostic approaches, prognostic significance, and treatment implications of ENE in NSCLC, analyzes existing challenges, and proposes future directions. The goal of this paper is to provide insights for optimizing clinical practice and guiding subsequent research.
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First-line immunotherapy for advanced non-small cell lung cancer (NSCLC) shows significant survival benefits in patients without driver mutations, but the optimal duration of treatment remains controversial. Some studies support limiting immunotherapy to 2 years, arguing that longer treatment does not bring additional survival benefits; while other studies believe that treatment should continue until disease progression to maximize survival benefits. This article systematically reviews the current research progress on the duration of immunotherapy and discusses the potential predictive value of biomarkers such as circulating tumor DNA (ctDNA), the best efficacy response, and programmed cell death ligand 1 (PD-L1) expression levels in individualized treatment decisions. More prospective studies, especially biomarker-driven trials, are still needed to clarify the optimal duration of treatment and establish an individualized treatment strategy based on multidimensional indicators.
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Small cell lung cancer (SCLC) is a highly aggressive neuroendocrine tumor. Although it accounts for only about 13% of all lung cancers, its rapid proliferation, early metastasis, and very poor prognosis result in an extremely low five-year survival rate. In recent years, immune checkpoint inhibitors have improved outcomes in a subset of patients; however, the proportion of patients who derive meaningful benefit remains limited. For patients with limited-stage SCLC (LS-SCLC) undergoing chemoradiotherapy (CRT), standardized serum biomarkers suitable for routine monitoring of treatment response and early detection of relapse have yet to be established. Progastrin-releasing peptide (ProGRP) is generally more specific than neuron-specific enolase (NSE) for SCLC, yet neither marker is diagnostic when used alone. This review summarizes the roles of ProGRP and NSE in LS-SCLC during chemoradiotherapy (CRT), with an emphasis on differential diagnosis (particularly when pleural effusion cytology suggests adenocarcinoma but ProGRP is markedly elevated-raising the possibility of SCLC, mixed histology, or transformation and underscoring the need for tissue confirmation), longitudinal monitoring, and prognostic implications. Notably, universally accepted cut-off values for survival prediction are lacking; therefore, clinical interpretation should focus on within-assay dynamic trends and incorporate potential interfering factors, including renal dysfunction and hemolysis.

Objective: To systematically summarize the research progress of clinical trials on breast cancer drugs in China from 2011 to 2022, as well as provide an overview of the marketed drugs. The goal is to offer data and decision-making evidence for relevant departments. Methods: Based on the registration database of the China National Medical Products Administration's Clinical Trial Registration and Information Disclosure Platform, as well as data from the domestic and imported drug query systems, an analysis was conducted on clinical trials of breast cancer drugs, including information on investigational drugs and marketed drugs from January 1, 2011, to December 31, 2022. The study compared differences between Chinese and foreign enterprises in terms of trial scope, trial phases, number of treatment lines, drug types, and mechanisms of action. Results: From 2011 to 2022, a total of 401 clinical trials for breast cancer were registered in China, accounting for 8.0% of the country's overall anti-tumor clinical trials (401/5 011), with 304 trials (75.8%) initiated by domestic enterprises. Over the past decade, clinical trials for breast cancer showed fluctuating growth, reaching a peak of 84 trials in 2020. These trials involved 254 drugs, with 156 (61.4%) being original drugs and 174 (68.5%) being targeted therapies. The most focused targets included human epidermal growth factor receptor 2 (HER-2), cyclin-dependent kinases 4/6 (CDK4/6), and estrogen receptors (ER). There are 50 drugs targeting HER-2 (28.7%), 35 targeting CDK4/6 (20.1%), and 31 targeting ER (17.8%). During the period from 2011 to 2022, a total of 15 drugs for treating breast cancer were approved and launched in China, covering 19 indications. Among these, 7 indications are for adjuvant or neoadjuvant therapy of early-stage breast cancer, and 12 indications are for advanced breast cancer. Conclusions: Substantial achievements have been made in the development of new breast cancer drugs in China from 2011 to 2022. However, there remains a significant gap in the innovation capabilities of domestic pharmaceutical companies compared to international counterparts in the field of breast cancer. Future efforts should be directed towards strengthening research and development in breast cancer, exploring new target points, and investigating combination therapy mechanisms.

Ocular tumors encompass ocular surface tumors, orbital tumors, and intraocular tumors, characterized by high heterogeneity and complex classifications, which pose considerable challenges to pathological diagnosis. The scarcity of specialized ophthalmic pathologists further exacerbates the difficulty in diagnosing these tumors. In recent years, artificial intelligence (AI) has penetrated diverse areas of healthcare, particularly in departments with intensive medical imaging and image-based workflows, such as radiology, pathology, and ultrasonography. With the advent of the digital pathology era, the role of AI in aiding pathological diagnosis has become increasingly prominent. In recent years, it has been tentatively applied to several ocular tumors, including eyelid sebaceous carcinoma, basal cell carcinoma, malignant melanoma, and orbital lymphoproliferative disorders, exerting an auxiliary diagnostic function. AI can also assist in predicting the prognosis of uveal malignant melanoma and retinoblastoma. In the future, with the increasing popularization and refinement of AI-assisted pathological diagnosis technologies, it will not only enhance the diagnostic accuracy and work efficiency of ocular tumors, better guide clinical treatment, but also alleviate the issues of inadequate medical resources and a shortage of specialized ophthalmic pathologists.

Objective: To explore the clinical features, diagnosis, and treatment progress of angiomatoid fibrous histiocytoma (AFH) primary to the pulmonary artery. Methods: A retrospective analysis was conducted on one case of AFH primary to the pulmonary artery in a middle-aged female. Databases including SinoMed, the Wanfang Data Knowledge Service Platform, and the China National Knowledge Infrastructure (CNKI) were searched using the keywords (angiomatoid fibrous histiocytoma) and (pulmonary artery). Meanwhile, PubMed, Embase, the Cochrane Library, and Web of Science were searched using the keywords "angiomatoid fibrous histiocytoma" and "pulmonary artery." The search was updated to April 2025. Results: The patient was admitted to our hospital in February 2025 due to symptoms such as chest tightness and dizziness, and a space-occupying lesion of the pulmonary artery was detected. Postoperative histopathological examination confirmed the diagnosis of pulmonary artery AFH. Only one relevant article was retrieved from domestic databases and five from foreign databases. A total of seven patients were included (including the current case), with four males and three females, aged 20-76 years (mean, 54.57±18.18 years). The lesions were located in the left main pulmonary artery (three cases), right main pulmonary artery (two cases), right upper pulmonary artery (three cases), and right interlobar pulmonary artery (one case). D-dimer levels were elevated in two cases, normal in three cases, and unknown in two cases. PET-CT showed significantly increased SUVmax in four cases and was unknown in three cases. EWSR1 gene translocation was detected in five cases, absent in one case, and unknown in one case. Surgical procedures included extended local resection of the pulmonary artery (three cases) and partial or total pneumonectomy (four cases). No recurrence or metastasis was observed in five patients, and the outcomes of two patients were unknown. Conclusion: AFH primary to the pulmonary artery is extremely rare. Clinically, it needs to be mainly differentiated from pulmonary thromboembolism and pulmonary artery intimal sarcoma, and clinicians in respiratory medicine and vascular intervention departments should raise awareness of this disease. In the differential diagnosis from pulmonary thromboembolism, clinical manifestations and laboratory tests (e.g., D-dimer) lack specificity, while imaging examinations such as CTPA and PET-CT are effective auxiliary methods. Definitive diagnosis still relies on histopathological examination, and EWSR1 molecular detection is an important basis for pathological confirmation. Pulmonary artery resection combined with artificial vascular replacement is an effective treatment, and long-term follow-up is necessary.

Pancreatic cancer(PC) is a highly malignant tumor of digestive system, and it is called "the king of cancer". Chronic pancreatitis(CP) is a high-risk factor for PC. The mechanism of "inflammation-cancer transformation" of CP and its prevention and treatment strategies are the focus of current research. Based on the second law of thermodynamics, the entropy disease theory reveals that the essence of disease is the disorder caused by the increase of entropy. The theoretical connotation of entropy disease is consistent with the pathogenesis of "inflammation-cancer transformation" in CP. The entropy disease theory clarifies that the "inflammation-cancer transformation" of CP is essentially an entropy-increasing process from a relatively orderly pathological state to a highly disordered cancerous state. In the initial stage, the spleen is weak with endogenous dampness accumulation, forming damp heat. This causes the disorder of energy metabolism and leads to the gradual increase of entropy value in the body. At the critical stage, phlegm and blood stasis stagnate each other, resulting in the microenvironment homeostasis imbalance of pancreatic tissue, which leads to the acceleration of the increase of entropy. In the qualitative change stage, the Qi in the body is blocked, and the cancer toxin is generated and accumulated, which leads to the collapse of the body's regulatory mechanism and the rise of entropy in the body until it breaks through the critical threshold. This eventually causes the formation of pancreatic cancer. In terms of treatment, this paper put forward a three-stage entropy reduction strategy for prevention and treatment, which involves clearing away dampness and heat, invigorating the spleen and regulating the stomach, resolving phlegm and eliminating stagnation, promoting blood circulation and removing blood stasis, and regulating the smooth operation of Qi and clearing away cancer toxin. These treatments can effectively block the occurrence of PC by correcting the disorder of energy metabolism, improving the imbalance of pancreatic microenvironment, and restoring the regulatory function of the body. Therefore, from the perspective of integrated traditional Chinese medicine and western medicine, this paper analyzed the internal relationship between entropy disease theory and "inflammation-cancer transformation" of CP, providing innovative ideas and a theoretical basis for early intervention and prevention of "inflammation-cancer transformation" of CP and holding important clinical application value and research significance.

The traditional paradigm of pathology diagnosis faces challenges like data fragmentation and inefficiency in the era of big data and artificial intelligence, necessitating a digital transformation built upon high-quality, standardized databases. This article reviews global efforts in digital pathology database construction and details our team's pilot practice in developing a specialized breast pathology database. We share our approach to case enrollment, systematic data collection, and standardized slide digitization. Key issues, including data schema design, multi-center integration, scanning protocols, and collaborative models, are discussed to inspire industry-wide standardization and support the sustainable development of digital pathology and artificial intelligence in China.

In breast pathology, tumor protein 63 (p63) is a highly sensitive and specific immunohistochemical marker for myoepithelial cells. It plays a crucial role in distinguishing benign from malignant diseases and in differentiating in situ carcinoma from invasive carcinoma. Aberrant p63 expression has also been increasingly recognized as a subject of clinical and diagnostic interest. A comprehensive understanding of the biological characteristics of p63, appropriate selection of antibodies, and its variable expression patterns across different breast diseases is essential for the accurate application and interpretation of p63 immunohistochemistry, enabling the avoidance of diagnostic pitfalls, minimizing misinterpretations, and ultimately supporting more precise pathological diagnosis.

Neuroendocrine tumors are rare, low-grade malignant tumors with a gradually increasing incidence rate in recent years, with gastroenteropancreatic neuroendocrine tumors being the most common among them. The majority of gastropancreatic neuroendocrine tumors have already metastasized to the liver at the time of initial diagnosis; therefore, treatment targeting liver metastases is crucial. The most effective treatment for hepatic metastases of gastropancreatic neuroendocrine tumors is surgical resection. However, 60%-70% of patients are ineligible for radical resection due to diffuse liver involvement. Thus, an alternative treatment option offered for these patients is liver transplantation. Liver transplantation is considered an indication for well-differentiated, unresectable hepatic metastases of gastropancreatic neuroendocrine tumors because of the tumor's low invasiveness, slow growth, and the fact that the liver is often the only distant metastasis site. This article reviews the research progress of liver transplantation therapy for hepatic metastases in gastropancreatic neuroendocrine tumors.

Tumor-associated macrophages (TAMs) are abundant immune cell content in the tumor microenvironment of hepatocellular carcinoma and are associated with tumor progression and therapeutic resistance. This article describes novel TAM subpopulations and potential targets in hepatocellular carcinoma that have been identified based on single-cell and spatial omics technologies. Additionally, it proposes TAMs' classification according to their functions into immunosuppressive, lipid-metabolizing, angiogenic, liver-resident, and immune-stimulating types and summarizes four major therapeutic strategies targeting TAMs, providing a reference for novel TAM-targeted therapies.

Tumor metastasis is the leading cause of cancer-related mortality. Disseminated tumor cells (DTCs), serving as the critical 'seeds' in the metastatic cascade, hold the key to determining the success or failure of metastasis. Following dissemination from the primary tumor and colonization of distant organs, DTCs often enter a prolonged state of dormancy. Their subsequent escape from immune surveillance through sophisticated mechanisms enables them to transition from this dormant state to a proliferative one, ultimately culminating in clinically detectable metastatic lesions. A profound understanding of DTCs immune evasion is therefore essential for unraveling the fundamental biology of metastasis and developing effective anti-metastatic strategies. This article systematically reviewed the latest advances in the mechanisms underlying DTCs immune evasion, focusing on three core aspects: defects in antigen presentation, formation of an immunosuppressive microenvironment, and metabolism reprogramming-mediated immunosuppression. Specifically, DTCs achieve 'immune invisibility' by downregulating major histocompatibility complex class-I (MHC-I) molecule expression; they actively construct a local 'protective shield' by recruiting immunosuppressive cells such as regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs); and they impair effector immune cell function at the energetic and metabolic levels by remodeling glucose, amino acid, and lipid metabolism. Building upon this, we innovatively integrate the traditional Chinese medicine (TCM) theories of 'hidden toxicity due to vital qi deficiency' and the 'metastatic state' to elucidate the dynamic pathogenic relationship between the body's systemic 'Zhengqi' (vital energy) status and the dormancy-awakening switch of DTCs, offering a novel holistic perspective for comprehending the metastatic process. Finally, we discussed the prospects of multi-target combination therapeutic strategies against DTCs immune evasion and highlight the potential of emerging technologies, such as single-cell sequencing and spatial transcriptomics, aiming to provide valuable insights for future in-depth research and clinical translation in the field of anti-metastasis therapy.
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Radiotherapy is an important treatment modality for tumors and is involved in the treatment course of more than 50% of cancer patients. However, resistance to ionizing radiation results in suboptimal radiotherapy efficacy and contributes to tumor recurrence and metastasis at later stages. With the increasing understanding of tumor pathogenesis, cancer stem cell (CSC), characterized by self-renewal capacity and differentiation potential, have attracted growing attention and play key roles in radiotherapy resistance, tumor progression, metastasis, immune evasion, and other processes. Mechanisms including the tumor microenvironment, DNA damage repair, and epithelial-mesenchymal transition (EMT) are critical drivers of CSC-mediated radiotherapy resistance. Reviewing the key pathways involved and identifying CSC-specific therapeutic targets may provide new insights for developing more efficient and less toxic radiotherapy strategies.

Breast cancer is one of the most common malignant tumors in women worldwide, and its high incidence and mortality rate seriously threaten women's health. Studies show that the forkhead box O3a (FoxO3a) plays a key role in the occurrence and progression of breast cancer, particularly in the regulation of apoptosis. As a major member of the FoxO family, FoxO3a exerts tumor-suppressive functions by participating in apoptosis regulation and cell-cycle control. In breast cancer cells, FoxO3a acts as a downstream signaling hub of multiple upstream pathways including phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT), mitogen-activated protein kinase (MAPK), and serum- and glucocorticoid-regulated kinase 1 (SGK1). Through nucleocytoplasmic shuttling and alterations in transcriptional activity, FoxO3a precisely modulates the expression of apoptosis-related target genes such as Bcl-2-interacting mediator of cell death (Bim) and p53-upregulated modulator of apoptosis (PUMA), thereby influencing cell survival or death. In addition, multiple natural compounds and combination therapies can induce apoptosis in breast cancer cells by restoring or enhancing FoxO3a activity, and may partially overcome treatment resistance. Systematic elucidation of the complexity of the FoxO3a signaling network and its dual roles in breast cancer therapy may provide theoretical support for understanding tumor-drug resistance mechanisms and for developing precision therapeutic strategies targeting FoxO3a nodes. Future research should further clarify the functional differences among FoxO3a splice variants and FoxO family members, reveal the molecular basis of FoxO3a functional switching in the tumor microenvironment, and promote the clinical translation of biomarkers and targeted drugs.

Aiolos is a member of the Ikaros zinc-finger protein family and is encoded by the Ikaros family zinc finger 3 (IKZF3) gene. Aiolos not only plays a crucial role in controlling the normal differentiation and proliferation of lymphocytes, but studies have also found that it exhibits abnormally high expression in the early stages of the onset and development of multiple tumors. It influences the biological behavior of tumor cells not only by regulating tumor invasion and metastasis through mediating signaling pathways such as 66-kilodalton Src homology 2 domain-containing transforming protein (p66Shc), phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/Twist, cellular myelocytomatosis oncogene, interferon regulatory factor 4, B-cell receptor, and nuclear factor kappa B, but also the instability of its gene affects tumor therapy, drug resistance, and patient prognosis. This suggests that IKZF3 is a good biological indicator for tumors and may become a new therapeutic target for tumors. A systematic elaboration of the latest research progress on the IKZF3 gene structure, physiological functions, tumor regulation, and treatment resistance can provide reference and scientific basis for future tumor therapy.