搜索结果：Cancer metastasis reviews

The construction of 3D in vitro tumor models centered on bioprinting technology represents one of the most anticipated interdisciplinary innovations and medical applications in recent years. Breakthrough research achievements have been made in the construction of 3D-printed models for various tumors, with a small subset of these technologies advancing to the clinical research stage. However, due to the complex behavioral characteristics of breast cancer bone metastasis, traditional research models exhibit significant limitations and yield minimal mechanistic insights into therapeutic interventions. The irreproducible spatiotemporal dynamics and complex, both synergistic and antagonistic, interactions of multicellular and biochemical components within the bone-metastatic breast cancer microenvironment, which remains irreproducible using conventional techniques, are precisely what drive the unique translational value of 3D bioprinting technology in clinical applications. This article systematically reviews recent advances and clinical explorations in 3D bioprinting technology for breast cancer models, with a focused analysis and summary of four key aspects: printable biomaterials, fabrication processes, research advantages, and translational applications. Capitalizing on recent advances in artificial intelligence (AI) technologies, this review provides a cross-disciplinary analysis of the current state of clinically oriented research and identifies critical challenges that must be addressed to achieve breakthroughs. Furthermore, it systematically summarizes the key difficulties and obstacles encountered across various research directions. Through this comprehensive review, we aim to provide biomedical engineers and clinicians with systematic insights and technical references regarding 3D bioprinted models of breast cancer bone metastasis, thereby facilitating the advancement of highly practical research in this field.

Lung cancer is one of the most common malignant tumors in the world, with a high incidence and a poor prognosis. The current treatment methods are limited, and novel treatment strategies are needed. Macrophages, as innate immune cells, interact with lung cancer cells in the tumor microenvironment and can influence the occurrence and development of lung cancer. This paper reviews the role of macrophages in lung cancer in relation to polarization, exosomes, cytokines, cell pathways and genes, and clinical prognosis. A structured literature search of PubMed, Web of Science Core Collection, and Embase was conducted from database inception to February 6, 2026. This was supplemented by cross-checking in Google Scholar and manual screening of reference lists from key reviews and landmark studies. Two authors independently screened titles and abstracts, and full texts were assessed according to designated inclusion criteria. A comprehensively review of the multifaceted roles of macrophages in lung cancer development, progression, and therapeutic response was conducted. The origin and phenotypic polarization of macrophages were examined, with the functional heterogeneity between antitumor M1 macrophages and protumor M2 tumor-associated macrophages (TAMs) within the tumor microenvironment emerging as a prominent topic. Another important theme was the crosstalk between macrophages and lung cancer cells mediated by exosomes, inflammatory cytokines, and key signaling pathways, including NF-κB, STAT3/STAT6, and PI3K/AKT, as well as gene regulatory mechanisms. These interactions collectively promote tumor growth, angiogenesis, metastasis, immune suppression, and therapy resistance. Furthermore, the clinical and prognostic significance of macrophage infiltration patterns and polarization status in patients with lung cancer was examined. Overall, the targeting of macrophage polarization and macrophage-related signaling networks emerged as a promising strategy for improving lung cancer diagnosis, prognosis assessment, and immunotherapeutic outcomes. Macrophages act as central regulators of lung cancer progression and therapeutic response through their remarkable plasticity within the tumor microenvironment. The balance between antitumor M1 and protumor M2 macrophages, shaped by exosomes, cytokines, signaling pathways, and gene regulation, critically influences tumor growth, metastasis, immune evasion, and prognosis. Targeting macrophage polarization and macrophage-related pathways represents a promising strategy for improving the diagnosis of patients with lung through achieving more accurate prognostic evaluation and greater treatment efficacy.

Lung cancer is the leading cause of cancer morbidity and mortality worldwide. A highly complex bidirectional regulatory relationship exists between lung cancer progression and the nervous system. The nervous system is believed to play a pivotal regulatory role in the genesis of lung cancer. It is involved in regulating malignant biological behaviors such as proliferation, local invasion, and distant metastasis of lung cancer cells via core mediating pathways involving neurons, neurotransmitters, and neuroactive molecules. At the same time, lung cancer itself and related therapeutic interventions are capable of inducing reverse structural and functional reprogramming within the nervous system. The emergence of cancer neuroscience as a novel interdisciplinary field offers a new perspective to overcome the current bottlenecks in lung cancer treatment, yet it also faces numerous theoretical and clinical challenges that urgently require resolution. This article systematically reviews the intricate relationship between the nervous system and lung cancer progression, focusing on the potential effects and molecular mechanisms of clinical strategies including local therapies, chemotherapy, immunotherapy, and targeted therapy on the nervous system, with the aim of clarifying research opportunities and key challenges in this field and providing a theoretical foundation and practical reference for optimizing the precision treatment system of lung cancer and improving clinical efficacy.
. 【中文题目：癌症神经科学视角下肺癌演进的
神经调控机制与临床治疗挑战】 【中文摘要：肺癌作为全球发病率与死亡率均居首位的恶性肿瘤，其演变进程与神经系统存在高度复杂的双向调控关系。神经系统在肺癌的起源阶段发挥关键调控作用，可通过神经元、神经递质及神经活性分子等核心介导途径，参与肺癌细胞增殖、局部侵袭及远处转移等恶性生物学行为的调控；与此同时，肺癌本身及相关治疗干预措施亦能反向诱导神经系统的结构重塑与功能重编程。癌症神经科学这一新兴交叉学科的崛起，为突破肺癌治疗瓶颈提供了全新的研究视角，但同时也面临诸多亟待解决的理论与临床挑战。本文系统梳理神经系统与肺癌演进的内在关联，重点剖析局部治疗、化疗、免疫治疗及靶向治疗等临床策略对神经系统的潜在影响及其分子机制，进一步明确该领域的研究机遇与核心挑战，旨在为优化肺癌精准治疗体系、提升临床治疗效能提供理论依据与实践参考。
】 【中文关键词：肺肿瘤；癌症神经科学；神经系统；神经活性分子】.

Cervical cancer (CC) is a major global health problem, and distant metastasis is a critical determinant of prognosis and survival. However, comprehensive data on the incidence and distribution of non-lymphatic distant organ metastases are limited. This systematic review and meta-analysis aimed to quantify the incidence of non-lymphatic distant organ metastasis in patients with CC and to identify the most commonly reported organ sites. A systematic search was conducted across PubMed/Medline, Web of Science, Scopus, and Embase from inception to March 1, 2025. To supplement the database searches and minimize publication bias, we also searched Google Scholar to identify potentially relevant studies. Reference lists of included studies were screened for additional eligible articles. Observational studies reporting the incidence or distribution of non-lymphatic distant organ metastases (bone, brain, liver, and lung) in CC cohorts were included. Case reports, reviews, and studies restricted exclusively to patients with established stage IVB/M1 disease at presentation were excluded, to avoid overrepresenting patients with already documented metastatic disease. Data were extracted using a standardized form. Pooled incidence rates per 100 patients with 95% confidence intervals (CIs) were calculated using a random-effects model. Heterogeneity was assessed using the I2 statistic. A total of 42 studies, comprising 238 387 patients, were included in the analysis. The pooled incidence rate of metastasis was 2.91 per 100 CC patients (95% CI: 2.84-2.97). Regional analysis showed that the Western Pacific region had the highest pooled incidence at 4.66 per 100 patients (95% CI: 4.52-4.79), followed by the European region at 2.50 per 100 patients (95% CI: 2.09-2.97) and the Americas at 1.68 per 100 patients (95% CI: 1.61-1.75). Among site-specific non-lymphatic distant organ metastases, bone was the most common, with a pooled incidence of 3.67 per 100 patients (95% CI: 2.37-5.06), followed by lung metastases (3.00 per 100 patients, 95% CI: 2.13-4.21), brain metastases (1.83 per 100 patients, 95% CI: 0.91-2.75), and liver metastases (1.70 per 100 patients, 95% CI: 0.45-2.95). Our findings indicate that the incidence of distant metastasis varies substantially by anatomic site, with bone and lung being the most common locations. However, due to large heterogeneity, these findings should be interpreted as descriptive trends rather than precise estimates. The predominance of bone and lung metastases emphasizes the need for enhanced clinical awareness regarding these organs and underscores the importance of standardized prospective studies to validate these patterns and guide surveillance strategies.

Cancer remains a major global health challenge, characterized by abnormal cell growth and metastasis. Current limitations of conventional therapies, particularly non-specific toxicity harming healthy cells, highlight the need for more targeted approaches. Nanotechnology offers a revolutionary solution, utilizing nanoparticles (NPs) for precise drug delivery to tumor sites while minimizing off-target effects. These nanometer-scale particles enable superior binding to cancer cell membranes, the tumor microenvironment, or nuclear receptors, facilitating significantly higher local concentrations of therapeutic agents. NPs, synthesized via physical, chemical, or biological methods, are categorized as organic (organic material-based) or inorganic (metallic particle-based). Key delivery mechanisms include the Enhanced Permeability and Retention (EPR) effect and Active Transport and Retention (ATR). This review specifically examines NP applications for the most prevalent cancers in the US (2025): breast, prostate, and lung. Gold and magnetic NPs show significant promise for early breast cancer detection. For lung cancer, polymeric NPs like PCL, PLA, and PLGA are effective carriers for peptides, proteins, and nucleic acids. BIND-014, a docetaxel-loaded NP formulation, represents an emerging strategy for prostate cancer. Clinically established examples include liposomal doxorubicin and albumin-bound paclitaxel. We comprehensively discuss the synthesis methods, delivery mechanisms, and the current landscape of NPs in research and clinical trials for these cancers. This analysis underscores the potential of nanotechnology to provide more effective and targeted therapeutic options for cancer patients in the future. A distinctive feature of this review is its comparative cancer-specific analysis of NP platforms in breast, prostate, and lung cancers. Unlike previous generalized reviews, this work integrates synthesis strategies, delivery mechanisms, translational challenges, and clinically relevant formulations to provide a bench-to-bedside perspective on the future of nanomedicine in oncology.

Although great progress has been achieved in radiotherapy,chemotherapy,and molecular targeted therapy for gastric cancer in recent years,the clinical benefits for patients with gastric cancer are very limited due to the high heterogeneity of gastric cancer.As the research on the immune microenvironment and the progression mechanism of solid cancers keeps advancing,accumulating evidence indicates that adoptive cell transfer therapy (ACT),as a novel precision therapy,holds important potential clinical applications in solid tumors such as gastric cancer.Chimeric antigen receptor T cell (CAR-T) therapy,T cell receptor-engineered T cell (TCR-T) therapy,natural killer (NK) cell therapy,etc.can inhibit the proliferation and metastasis of gastric cancer cells by conjugating specific antigen recognition components with T cells,genetically engineering T cells,and expanding and reinfusing NK cells in vitro.They exhibit particularly favorable therapeutic effects in patients with unresectable and metastatic gastric cancer.This article reviews the therapeutic principles,classification,main targets,and current treatment status of ACT and explores the opportunities and challenges it faces in the precision treatment of advanced gastric cancer,aiming to provide new ideas for the clinical treatment of gastric cancer. 尽管近年来放化疗和分子靶向治疗在晚期胃癌的治疗中取得了长足进展,但由于胃癌本身的高度异质性,胃癌患者临床获益十分有限。随着对免疫微环境与实体癌演进机制的研究不断深入,越来越多的证据表明,过继细胞疗法(ACT)作为一种新型精准疗法,在胃癌等实体瘤中具有重要的潜在临床应用价值。嵌合抗原受体修饰T细胞(CAR-T)、细胞受体工程T细胞(TCR-T)和NK细胞疗法等可以通过将特定抗原识别部分与T细胞结合、基因工程改造T细胞、体外扩增回输NK细胞等方式来抑制胃癌细胞增殖和转移,特别是在不可切除以及转移性胃癌患者中具有较好的疗效。本文总结了ACT的治疗原理、分类、主要靶点及治疗现状,探讨了其在晚期胃癌精准治疗中面临的机遇与挑战,旨在为胃癌的临床治疗提供新的思路。.

Primary bone cancer is a relatively rare malignant tumor that manifests in the bone and affects the normal functioning of the bone tissue. Primary bone cancer can be characterized into three subtypes, which are osteosarcoma, chondrosarcoma, and Ewing sarcoma. Notably, the treatment of primary bone cancer with conventional modalities, like chemotherapy and surgical interventions, has been overwhelmed with dismal clinical outcomes. The conventional therapies are challenged with non-specificity, resulting in off-target effects and ultimate harm to healthy tissue. Particularly, chemotherapy as a first-line treatment option is riddled with poor drug bioavailability, limited tumor accumulation, and increasing drug resistance. Several innovative drug delivery systems, including nano-based carriers, have been investigated to overcome the systemic drug delivery challenges in primary bone cancer. Accordingly, with most reviews focusing on bone metastasis (secondary bone cancer), this current narrative review aims to provides critical insights on nanocarrier strategies for drug delivery in primary bone cancer, comprehensively expounding on the epidemiology, cellular mechanisms, and etiological effects of primary bone cancer, as well as the current therapies and new drug nanocarriers prototyped to optimize the clinical outcomes in bone cancer management.

Determination of lymph node metastasis is crucial for prognosis and treatment strategies for gynecologic cancers. Assessing metastases using a sentinel lymph node biopsy (SLNBx) approach decreases surgical morbidity and improves quality of life. This review evaluates the efficacy, safety, and clinical utility of SLNB in gynecologic cancers to inform clinical practice and highlight areas for future research. Endometrial, vulvar, cervical, and ovarian cancer studies on SLNB were obtained from databases including PubMed, Scopus, and Web of Science. The search focused on peer-reviewed articles, systematic reviews, meta-analyses, clinical practice guidelines, and expert consensus statements published in English. SLNBx is an effective alternative to systematic lymphadenectomy for staging gynecologic malignancies. It is established for vulvar and endometrial cancer staging. For cervical cancer, the SENTICOL and SENTIX studies demonstrate high detection rates and comparable survival outcomes to lymphadenectomy with fewer comorbidities. In ovarian cancer, SLNBx detection rates vary, and additional research is needed to determine the role of SLNBx. Clinical studies support the use of SLNBx for staging of endometrial, vulvar, and cervical cancers. Future research and standardized protocols are essential to establish SLNBx as a standard practice in ovarian cancer.

Leptomeningeal metastasis (LM) from non-small cell lung cancer (NSCLC) is a devastating complication associated with a poor prognosis, with historical median overall survival (OS) of approximately 3-6 months. Limited penetration of systemic therapies across the blood-brain and blood-cerebrospinal fluid (CSF) barriers has prompted increasing interest in intrathecal (IT) drug delivery. The Ommaya reservoir, an implantable ventricular access device, provides a practical route for achieving therapeutic drug concentrations within the CSF and has been increasingly applied in NSCLC-related LM. To systematically review contemporary evidence regarding the efficacy, safety, and delivery-route considerations of intrathecal (IT) therapy in NSCLC-related LM, with particular emphasis on the clinical role of Ommaya reservoir-based delivery. A comprehensive literature search of PubMed, MEDLINE, Embase, Scopus, Web of Science, the Cochrane Library, and CNKI was conducted from database inception to September 30, 2025. Original studies reporting clinical outcomes of intrathecal chemotherapy and/or targeted therapy in adult patients with NSCLC-related LM were reviewed in accordance with PRISMA 2020 guidelines. Delivery route (Ommaya reservoir vs lumbar puncture) was extracted when reported. Studies without extractable NSCLC-LM-specific clinical outcome data and narrative reviews/guidelines were excluded from the primary clinical efficacy synthesis and used for contextual background only. Ten original studies met predefined criteria for NSCLC-specific clinical efficacy synthesis. Across these studies, intrathecal therapy was associated with neurological improvement and CSF cytology clearance in a substantial proportion of patients. Traditional IT agents such as methotrexate or cytarabine were generally associated with modest survival outcomes, whereas more recent studies evaluating IT pemetrexed and molecularly guided regimens reported longer survival in selected cohorts, particularly in EGFR-mutant NSCLC-LM. Studies using Ommaya reservoir-based delivery highlighted practical advantages in repeated CSF access and treatment continuity, while device-related complications (e.g., infection and catheter malfunction) were generally manageable. However, most available evidence derives from retrospective, single-center cohorts with heterogeneous treatment protocols, and randomized comparative evidence remains limited. Intrathecal therapy represents an important component of multimodal management for selected patients with NSCLC-related LM. Ommaya reservoir-based delivery may offer practical advantages for repeated treatment and CSF monitoring in appropriately selected patients, with acceptable toxicity and manageable device-related risks. Emerging data on pemetrexed-based intrathecal regimens and other molecularly informed approaches suggest potential benefit in selected subgroups, but prospective, multicenter, mutation-stratified studies are needed to refine patient selection, optimize dosing strategies, and define the comparative role of different intrathecal delivery routes.

Microtubules are essential cytoskeleton polymers composed of α/β-tubulin heterodimers that play a central role in the regulation of various cellular processes, including cell division, cell shape, cell polarity, motility and intracellular trafficking. The expression of different tubulin genes results in a variety of isotypes that, combined with post-translational modifications (PTMs), define a "tubulin code" that generates microtubule diversity. Growing evidence has shown promising links between tubulin isotypes and PTMs with several cancer properties, leading to the emergence of the concept of a "cancer tubulin code". In this review, we focus on dissecting the impact of tubulin acetylation, detyrosination and polyglutamylation on microtubule properties and functions, and how these PTMs, together with specific tubulin isotypes, affect cancer cell division, invasion and metastasis. Because conventional chemotherapy with microtubule-targeting drugs often leads to resistance and accounts for a high mortality rate among cancer patients, we discuss possible directions that explore the potential of the cancer tubulin code and respective microtubule diversity in improving drug response, while overcoming resistance. Lastly, we address the therapeutic value of small-molecule inhibitors of tubulin-modifying enzymes in cancer treatment. Overall, this review showcases the potential of exploring the cancer tubulin code to open new avenues in diagnostic, prognostic and therapeutic applications for precision oncology.

Epidemiological and preclinical studies are discrepant regarding the role of psychosocial stress in breast cancer (BC) development and metastasis. While no consensus has been reached based on epidemiological studies, preclinical rodent studies regularly employ chronic psychosocial stress paradigms to study mechanistic details in mammary carcinogenesis and metastasis. We aimed to review both epidemiological and preclinical studies of psychosocial stress in BC development, focusing on whether chronic psychosocial stress might be a particularly relevant stressor domain. For in vivo preclinical rodent studies, we searched PubMed for individual studies from 1985 to December 2025 written in English that evaluated effects of chronic psychosocial stress on mammary tumorigenesis and metastasis. We restricted focus to studies that used chronic psychosocial stress protocols. For epidemiological research into psychosocial stress in BC, due to the abundant literature that spans several decades, we searched Medline (PubMed) for English-language systematic reviews and meta-analyses published in the last three decades (1995 to December 2025) in which participants were inquired about exposure to psychosocial stress. Systematic literature searches identified 29 rodent studies that randomly allocated rodents to chronic psychosocial stress or safety. Twenty-five of the 29 studies found that chronic psychosocial stress increased mammary tumorigenesis and/or metastasis, with the remaining studies reporting more complex effects that reflected variations in study design elements. In contrast, most original research studies included in 14 systematic reviews and meta-analyses of epidemiological research focused on short-lasting, adverse life events, with no consistent associations detected with BC. Epidemiological studies have only partly and unsystematically addressed chronic psychosocial stress. Findings from preclinical rodent studies indicate that chronic psychosocial stress may be a particularly relevant psychosocial exposure domain in BC development. In contrast, the epidemiological studies we reviewed focused predominantly on acute adverse life events, with limited attention to chronic psychosocial stress. We suggest that this evidence highlights the need to prioritize chronic psychosocial stress in future epidemiological studies of BC etiology. Actionable method components may include a life-course perspective for stress exposure, a multi-level social interaction perspective, inclusion of both chronic and acute stress and their interactions, and inclusion of individuals' subjective appraisals of distress.

Pancreatic ductal adenocarcinoma (PDAC) is associated with poor overall survival and is largely refractory to standard therapies. Most patients present with locally advanced or metastatic disease, and those with early-stage tumors amenable to surgical resection face high rates of metastatic relapse. Despite the many successes of immunotherapy in other solid tumors, these approaches have shown only marginal activity in PDAC. In PDAC, metastasis occurs through a coordinated, multistep process characterized by a gradient loss of immune surveillance. This process begins with establishment of a receptive premetastatic niche, which occurs via conditioning of distant tissues by tumor-derived exosomes and the recruitment of myeloid cells, leading to extracellular matrix remodeling and local immunosuppression prior to metastatic dissemination. On arrival of metastatic cells, tissues undergo organ-specific immune editing with important implications for therapeutic vulnerability. Importantly, liver metastases maintain a profoundly immunosuppressive environment whereas lung metastases have higher immune activity. These observations challenge the prevailing assumption that insights from primary tumors are broadly applicable to metastatic disease, establishing metastatic PDAC as a distinct immunologic entity. This framework identifies unique therapeutic opportunities across the disease spectrum from early interventions targeting premetastatic niche formation to site-specific strategies for established metastatic disease.

Polysaccharides comprise a structurally varied class of natural macromolecules found in plants, fungi, animals, marine algae, and microorganisms. Therefore, they have attracted considerable attention over several decades due to numerous anticancer-associated activities indicated by accumulating in vitro and in vivo evidence, along with clinical data of heterogeneous maturity-ranging from well-established adjuvants such as lentinan and PSK, which have demonstrated survival benefits in randomized controlled trials, to early-phase exploratory studies for agents like fucoidan. Traditional chemotherapeutic agents (e.g., alkylating agents, antimetabolites) exert direct cytotoxic effects; however, many contemporary small-molecule drugs-such as kinase inhibitors and hormone receptor modulators-act through targeted inhibition of oncogenic signaling, and immunotherapies (e.g., checkpoint inhibitors) function by enhancing endogenous anti tumor immunity rather than directly damaging tumor cells, as cytotoxic agents do. By contrast, polysaccharides are increasingly recognized as biological response modifiers that exert an impact on cancer development through, for instance, immune system functioning, redox, and/or inflammatory balance, communications between cancer and stromal cells of the tumor microenvironment, and intracellular signaling cascades. This review presents an outline of the structural variability, physiological sources, and functions of polysaccharides relevant to cancer treatment. Based on the present armamentarium of polysaccharides, the main modes of action are summarized in terms of immunomodulation through the engagement of pattern-recognition receptors, oxidative stress and inflammation regulation, quantifiable programmed cell death modes, angiogenesis and metastasis, and indirect regulation of oncogenic signaling pathways. These are first expressed in terms of the target-unrelated context and at the network level. Finally, we briefly discuss recent developments regarding polysaccharides as coadjuvants in chemotherapy, radiotherapy, and immunotherapy, in addition to their status as potential biomaterials in novel drug delivery systems. Critical reviews of relevant issues regarding structural heterogeneity and reproducibility, pharmacokinetics, and clinical translation are given. Indeed, this review presents polysaccharides as multi-functional components in multi-dimensional cancer therapy, paying due attention to appropriate structural elucidation, mechanism validation, and systems-oriented approaches to their rational development and clinical application.

Multicellular organisms are not just collections of cells; they are evolutionary compromises in which cell-level fitness is subordinated to organism-level integrity. Cancer begins when that compromise is locally subverted, but metastasis is the decisive escalation: malignant cells must cross tissue boundaries, survive a hostile systemic phase, condition remote organs, enter or escape dormancy and construct a new permissive ecology. This Perspective uses the social-contract metaphor as a disciplined heuristic, not as a claim of intention or moral agency, to integrate metastasis biology with eco-evolutionary thinking. We argue that the metastatic cascade can be read as serial failure of multicellular governance: local architecture loses territorial control; vascular and immune systems fail to exclude or destroy emigrant cells; distant tissues become preconditioned by tumour-derived signals; dormant disseminated cells persist as residual insurgencies and colonisation emerges when organ-specific restraint is converted into support. The framework becomes most useful when it also explains the paradox that cells which defect from host-level cooperation may cooperate locally with each other and with recruited stroma. Public goods, collective dissemination, metabolic exchange and premetastatic niche construction create dependencies that may be exploitable therapeutically. We give the Black Queen Hypothesis a precise but bounded role: it is a testable model for dependency-generating loss or outsourcing of costly shared functions, not a universal law of cancer evolution. Finally, we outline translational implications for metastasis: rearming immune enforcement, blocking niche education, maintaining or eradicating dormant disease, disrupting shared dependencies and using adaptive schedules to manage evolutionary escape. The social-contract lens is valuable only when it remains evidence-led and mechanistically anchored; used this way, it makes metastatic dormancy and colonisation a sharper target for ecological cancer therapy.

Evidence from experimental studies suggests that pain may influence cancer development. We conducted a systematic review (registration osf.io/ms437) of the epidemiological studies assessing whether chronic pain, with minimal or non-inflammatory features, increases the risk of cancer incidence or mortality. The search used Scopus and Web of Science up to 11/03/2025. Quality assessment used the Newcastle-Ottawa Scale. Study characteristics and outcomes were analysed using narrative synthesis, with random-effects meta-analysis and meta-regression conducted where appropriate. A total of 23 studies (12 prospective, 11 retrospective) met the inclusion criteria, of which six were rated as high quality. The outcome data synthesis indicates a small increase in cancer mortality rate ratios, and a potential increase in a subset of organs. A total of three body site-specific analyses suggest that chronic pain may be associated with higher incidence for breast (SIR 2.12-4.8) and prostate (SIR 1.49-5.59) cancers, and with increased mortality for lung cancer (MRR 3.09, 95% CI 1.45-6.62). Ten studies were included for meta-analysis, including four studies rated as high quality. Meta-analysis of hazard ratios showed no association between cancer-related mortality and pain (HR 1.00, 95% CI 0.97-1.04), with consistent estimates across pain subtypes in meta-regression. Our review and meta-analysis do not support an overall association between chronic pain and increased risk of cancer mortality or incidence and highlight multiple methodological and conceptual obstacles to exploring this relationship, including reverse causation and confounding factors such as pain and opioid use association. High-quality studies that rigorously address reverse causation and confounding are warranted.

Sphingosine-1-Phosphate (S1P) is a bioactive phospholipid molecule that regulates multiple signaling pathways through its interaction with sphingosine-1-phosphate receptors (S1PRs). In cancer tissues, S1P is not only associated with the survival of cancer cells, but also related to the angiogenesis, inflammatory responses, and immune evasion in the tumor microenvironment (TME). Various inhibitors of the S1P kinase have shown significant anti-tumor effects in pre-clinical studies by directly inhibiting tumor growth and metastasis, and enhancing the therapeutic potential of both chemotherapy and immunotherapy. Nevertheless, the complex and pleiotropic nature of the S1P signaling pathway presents considerable challenges for the development of targeted therapeutic strategies. This paper reviews the biological functions and research progress of S1P and its related pathways in cancer, offering novel insights and potential directions for cancer therapy.

The objective of this systematic review and meta-analysis was to estimate the incidence of lymph node metastasis among patients with clinically early-stage (International Federation of Gynecology and Obstetrics 2014 stage I-IIA) low-grade serous ovarian carcinoma undergoing primary surgical treatment. Registered in International Prospective Register of Systematic Reviews (CRD420251165472), this systematic review was conducted in accordance with the Meta-analysis of Observational Studies in Epidemiology guidelines. We searched Ovid MEDLINE, Embase, and Web of Science from inception through September 2025. Eligible studies included patients with pathologically confirmed low-grade serous ovarian carcinoma who were clinically presumed to have International Federation of Gynecology and Obstetrics 2014 stage I to IIA disease at surgery and underwent primary surgical management with pelvic and/or para-aortic lymph node dissection. We conducted a meta-analysis of single proportions to estimate the pooled rate of lymph node metastasis. Study-specific proportions (events/total) were pooled using an inverse-variance random-effects model with Freeman-Tukey double-arcsine transformation and back-transformed to proportions with 95% confidence intervals. Subgroup analyses excluded registry-based studies, studies at high risk of bias, and stage II disease. Among 129 screened records, 8 studies met the inclusion criteria after full-text review. Overall, 77 patients had lymph node metastasis, corresponding to a pooled incidence of lymph node metastasis of 9.6% (95% confidence interval 4.4% to 16.0%; I2 58.8%). In the 3 studies reporting stage migration attributable only to nodal disease, 16 of 153 patients were upstaged, yielding a pooled upstaging proportion of 10.0% (95% confidence interval 5.6% to 15.5%; I2 30.6%). Subgroup analyses showed no statistically significant differences associated with these factors. None of the included studies provided perioperative complication rates for lymphadenectomy. Approximately 1 in 10 patients with clinically early-stage low-grade serous ovarian carcinoma harbors occult nodal metastasis. These findings support discussing lymph node assessment as a source of staging information during preoperative counseling and individualized surgical planning. The prognostic and therapeutic value of identifying isolated nodal disease and the morbidity trade-offs in this setting remain unclear.

Extracellular vesicle (EV)-derived proteins are increasingly investigated as liquid biopsy biomarkers because they can reflect tumour-associated molecular processes in clinically accessible biofluids. However, their diagnostic performance and methodological robustness in breast cancer remain incompletely defined. This study evaluated EV-derived protein biomarkers for breast cancer diagnosis through a systematic review and meta-analysis of primary studies, complemented by an umbrella review of published systematic reviews and meta-analyses. A structured search was conducted in PubMed/MEDLINE, Web of Science, and Scopus from database inception to February 2026 and subsequently updated during revision. Primary studies assessing EV-derived proteins or proteomic signatures in clinically relevant biofluids and reporting diagnostic performance metrics were eligible for quantitative synthesis. Methodological quality was assessed using QUADAS-2, and the quality of secondary reviews was evaluated with AMSTAR 2. Six independent studies were included in the meta-analysis. The pooled area under the receiver operating characteristic curve was 0.90 (95% CI 0.86-0.94), indicating high discriminatory capacity. However, the estimate should be interpreted cautiously because of the limited number of studies and substantial heterogeneity (I2 = 84.6%). The umbrella review identified four main functional domains: diagnostic applications, therapeutic resistance, tumour progression and metastasis, and global proteomic characterisation. EV-derived protein biomarkers show potential for breast cancer diagnosis, but current evidence is limited by methodological heterogeneity, incomplete analytical standardisation, and the lack of clinically actionable thresholds. Future progress will depend on harmonised pre-analytical and analytical protocols, multicentre validation, and diagnostic frameworks supporting their potential implementation in clinical laboratory practice.

Introduction: Axillary lymph node dissection (ALND) has been the gold standard for axillary staging in breast cancer for over a century. The introduction of sentinel lymph node biopsy (SLNB) in the 1990s offered a minimally invasive alternative with comparable staging accuracy and significantly reduced morbidity. Multiple landmark randomized controlled trials have since demonstrated that completion ALND can be safely omitted in selected patients with positive sentinel lymph nodes without compromising oncologic outcomes. This narrative review aims to examine the evolution from ALND to SLNB, critically evaluate the landmark trials that shaped current practice, and discuss ongoing controversies and future directions in axillary management in early breast cancer. Materials and Methods: A comprehensive literature search was performed using PubMed/MEDLINE, Scopus, and Web of Science databases. Search terms included "sentinel lymph node biopsy", "axillary lymph node dissection", "breast cancer", and "axillary management." Landmark randomized controlled trials, systematic reviews, meta-analyses, and current clinical practice guidelines were identified and reviewed. Results: The NSABP B-32 trial validated SLNB as an accurate staging tool equivalent to ALND. The ACOSOG Z0011 trial demonstrated no survival benefit from completion ALND in patients with 1-2 positive sentinel lymph nodes undergoing breast-conserving surgery. The AMAROS trial demonstrated that irradiation of the axilla provides equivalent locoregional disease control compared to surgical dissection, while carrying a substantially more favorable morbidity profile.The IBCSG 23-01 trial confirmed that ALND can be omitted for sentinel node micrometastases. Most recently, the SENOMAC trial extended these findings to patients with 1-2 macrometastases in a broader population. Conclusions: SLNB has become the established standard for axillary staging in early breast cancer with a clinically negative axilla, superseding ALND entirely. Progressive de-escalation of axillary surgery has been consistently supported by high-level evidence without compromising survival. Future research will determine the feasibility of further de-escalation, particularly after neoadjuvant chemotherapy.