Current Oncology Reports最新文献

{"title":"Periodontitis as a Modulator of Malignant Transformation in Oral Potentially Malignant Disorders: A Narrative Review of Biological Mechanisms and Clinical Implications.","authors":"Giorgia Pieretto, Martina Sansavini, Arthur Rodriguez Gonzalez Cortes, Christian Bacci","doi":"10.1007/s11912-026-01817-z","DOIUrl":"10.1007/s11912-026-01817-z","url":null,"abstract":"<p><strong>Purpose of review: </strong>Oral potentially malignant disorders (OPMDs) comprise a heterogeneous group of lesions with a variable risk of progression to oral squamous cell carcinoma (OSCC). Although conventional risk assessment relies primarily on clinical and histopathological features, increasing evidence suggests that the local oral microenvironment may also influence malignant transformation. This narrative review examines the potential role of periodontitis as a modulator of OPMD progression, with particular emphasis on the underlying biological mechanisms and clinical implications. A targeted literature search was conducted in PubMed/MEDLINE, Scopus/EMBASE, and Web of Science for studies published between January 2000 and March 2026.</p><p><strong>Recent findings: </strong>Available evidence suggests that periodontitis may promote a pro-tumorigenic oral microenvironment through the interconnected effects of chronic inflammation, microbial dysbiosis, and metabolic alterations. These processes may enhance epithelial proliferation, genomic instability, immune evasion, and field cancerization, potentially facilitating the progression of OPMDs to OSCC. Although direct longitudinal and interventional evidence remains limited, converging mechanistic, biological, and epidemiological findings support the hypothesis that periodontal disease may contribute to early oral carcinogenic processes. Periodontitis may represent an underrecognized component of oral cancer risk, particularly in patients with OPMDs. Incorporating periodontal assessment into their clinical management may support more comprehensive risk stratification. Although causality has not been established, controlling periodontal inflammation and dysbiosis may offer a potential preventive strategy. Further longitudinal and interventional studies are required to determine the clinical relevance of this association.</p>","PeriodicalId":10861,"journal":{"name":"Current Oncology Reports","volume":"28 1","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13498645/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148789262","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early-Onset Colorectal Cancer: From Epidemiologic Shift to Life-Course Carcinogenesis and Age-Attuned Care.","authors":"Magda Grześkiewicz-Szostak, Katarzyna Gęca, Magdalena Skórzewska","doi":"10.1007/s11912-026-01815-1","DOIUrl":"https://doi.org/10.1007/s11912-026-01815-1","url":null,"abstract":"<p><strong>Purpose of review: </strong>Early-onset colorectal cancer (EOCRC), conventionally defined as colorectal cancer diagnosed before the age of 50 years, has become one of the most important and unsettling epidemiologic shifts in gastrointestinal oncology. This review critically synthesizes recent evidence on EOCRC epidemiology, risk architecture, life-course carcinogenesis, molecular and microbiome-associated mechanisms, diagnostic delay, screening limitations, treatment considerations, and survivorship needs, with the aim of reframing EOCRC as an age-attuned clinical and biological challenge rather than a simple early presentation of conventional colorectal cancer.</p><p><strong>Recent findings: </strong>Recent population-based analyses confirm that EOCRC incidence is increasing across multiple countries and birth cohorts, with a disproportionate contribution of distal colon and rectal cancers. These data suggest that the rise of EOCRC is unlikely to be explained by improved detection alone and instead points toward changing generational exposures. Contemporary studies have moved the field beyond hereditary predisposition as the dominant explanatory model: although germline syndromes remain essential to identify, most EOCRC is sporadic or incompletely explained by known inherited risk. Recent literature increasingly implicates metabolic dysfunction, obesity, westernized dietary patterns, early-life exposures, inflammation, antibiotic-associated microbial disruption, and host-microbiome disequilibrium. Particularly important are emerging genomic data linking colibactin-associated mutational signatures to younger-onset disease, supporting the hypothesis that microbial genotoxicity may imprint early driver events long before clinical diagnosis. In parallel, recent clinical studies show that EOCRC is frequently symptomatic, yet diagnosis is commonly delayed because alarm features such as rectal bleeding, abdominal pain, altered bowel habits, and anaemia are often underestimated in younger adults. EOCRC is best understood as a heterogeneous, life-course disease shaped by the convergence of inherited susceptibility, environmental and metabolic exposures, microbiome-mediated biology, tumour site, diagnostic-system factors, and survivorship context. Lowering the average-risk screening age to 45 years is necessary but insufficient, because many cases still occur below routine screening thresholds. A modern EOCRC strategy must therefore combine risk-adapted prevention, improved family-history capture, timely investigation of red-flag symptoms, systematic germline and tumour profiling, and treatment planning that accounts for decades of survivorship. Future progress will depend on moving beyond age alone toward integrated models that connect epidemiology, exposome biology, microbial mutagenesis, precision early detection, and age-specific care.</p>","PeriodicalId":10861,"journal":{"name":"Current Oncology Reports","volume":"28 1","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13490218/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148789244","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Letter: Advances in Radiotherapy for Soft Tissue Sarcomas in 2025: A Review.","authors":"G F Foppele, R L M Haas, L M Wiltink","doi":"10.1007/s11912-026-01813-3","DOIUrl":"10.1007/s11912-026-01813-3","url":null,"abstract":"","PeriodicalId":10861,"journal":{"name":"Current Oncology Reports","volume":"28 1","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148677476","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunotherapy Resistance in Pancreatic Ductal Adenocarcinoma: from Tumor Biology to Biomarker-Guided Strategies.","authors":"Layal Al Mahmasani, Mohamad Mourad, Noura Abbas, Ali Shamseddine","doi":"10.1007/s11912-026-01812-4","DOIUrl":"10.1007/s11912-026-01812-4","url":null,"abstract":"<p><strong>Purpose of review: </strong>Despite major advances inimmunotherapy, pancreatic ductal adenocarcinoma (PDAC) remains one of the most immunotherapy-resistant solid tumors. This review aims to summarize the key biological mechanisms underlying immune resistance in PDAC and to evaluate established and emerging biomarkers that may guide immunotherapy strategies.</p><p><strong>Recent findings: </strong>Resistance to immunotherapy in PDAC arises from the interplay of tumor-intrinsic oncogenic signaling, low antigenicity, defective antigen presentation, and a profoundly immunosuppressive tumor microenvironment characterized by dense desmoplasia, hypovascularity, metabolic competition, and enrichment of regulatory T-cells, myeloid-derived suppressor cells, tumor-associated macrophages, and cancer-associated fibroblasts. While MSI-H/dMMR and high tumor mutational burden identify small subsets of patients who may benefit from immune checkpoint blockade, most other biomarkers, including PD-L1 expression, homologous recombination deficiency, KRAS-related immune phenotypes, and circulating markers such as ctDNA and exosomal PD-L1, remain investigational or primarily prognostic. Emerging data highlight the importance of transcriptomic, spatial, and composite biomarker approaches to better capture tumor-immune interactions. PDAC exhibits a complex and actively maintained state of immune resistance that cannot be overcome by checkpoint inhibition alone. Future progress will depend on biomarker-guided combination strategies targeting oncogenic pathways, stromal barriers, and innate immune suppression, along with prospective validation of integrated, multimodal biomarker models to advance precision immuno-oncology in PDAC.</p>","PeriodicalId":10861,"journal":{"name":"Current Oncology Reports","volume":"28 1","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148668552","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Application and Advancement of Herbal Medicine in Gastrointestinal Cancers: A Bibliometrix Visualization and Pan-cancer Analysis.","authors":"Lingyun Zhao, Heng Wang, Yuchen Jiang, Ziming Zhao, Qiuyu Liang, Yu Li, Jue Wang, Wenwei Zhong, Yuan Xu, Xiaotian Zeng, Taorui Liu, Yuqin Yang, Qibiao Wu, Keyang Xu","doi":"10.1007/s11912-026-01811-5","DOIUrl":"10.1007/s11912-026-01811-5","url":null,"abstract":"<p><strong>Introduction: </strong>Herbal medicine has emerged as an important area of investigation in gastrointestinal cancers owing to its multitarget therapeutic potential and growing integration with modern oncology. However, the rapid expansion of the literature has resulted in a fragmented understanding of the field's knowledge structure, research evolution, and emerging directions.</p><p><strong>Methods: </strong>A bibliometric analysis was performed using publications retrieved from the Web of Science Core Collection between 2016 and 2025. Bibliometrix, VOSviewer, and CiteSpace were employed to evaluate publication trends, collaboration networks, thematic evolution, and knowledge foundations. To further assess the biological relevance of major research themes, representative molecular markers associated with apoptosis, cell-cycle regulation, and epithelial biology were examined using transcriptomic data integrated from The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) project through the Gene Expression Profiling Interactive Analysis (GEPIA) platform.</p><p><strong>Results: </strong>A total of 1,985 publications were included. Research activity increased substantially over the study period, particularly after 2020. Bibliometric analyses revealed a progressive transition from traditional investigations of apoptosis, proliferation, and metastasis toward emerging themes involving tumor microenvironment regulation, ferroptosis, gut microbiota interactions, network pharmacology, and molecular docking. Knowledge structure analyses demonstrated increasing integration of experimental oncology, bioinformatics, and traditional Chinese medicine research. China dominated global publication output, while the United States exhibited the strongest international collaborative profile. Exploratory transcriptomic validation showed that representative molecular markers (BCL2, CCND1, and CDH1) exhibited differential expression patterns across multiple gastrointestinal malignancies, supporting the biological relevance of the dominant research themes identified through bibliometric analyses.</p><p><strong>Conclusion: </strong>Research on herbal medicine for gastrointestinal cancers is transitioning from descriptive pharmacological investigations toward mechanism-oriented, data-driven, and translational research. By integrating bibliometric visualization with exploratory pan-gastrointestinal-cancer transcriptomic validation, this study provides a comprehensive overview of the field's evolution and offers a complementary framework linking knowledge mapping with molecular-level evidence. These findings provide biological context for emerging research priorities and may facilitate future biomarker discovery and precision-oriented herbal medicine research for gastrointestinal cancers.</p>","PeriodicalId":10861,"journal":{"name":"Current Oncology Reports","volume":"28 1","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148618626","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Follicular Lymphoma: Novel Therapies and Strategies for Optimal Therapeutic Sequencing.","authors":"Rodrigo Fonseca, Talal Hilal","doi":"10.1007/s11912-026-01803-5","DOIUrl":"10.1007/s11912-026-01803-5","url":null,"abstract":"<p><strong>Purpose of review: </strong>Follicular lymphoma (FL) is the most common indolent non-Hodgkin lymphoma, characterized by a relapsing and remitting course and a median overall survival exceeding 15-20 years with modern therapy. While chemoimmunotherapy remains the cornerstone of frontline management, the rapid approval of novel agents, including bispecific antibodies, CAR T-cell products, and antibody-drug conjugates, has fundamentally reshaped the relapsed/refractory (R/R) landscape. This review summarizes current evidence across the treatment continuum and propose a practical, risk-adapted sequencing framework.</p><p><strong>Recent findings: </strong>Bispecific antibodies (mosunetuzumab, epcoritamab) have demonstrated durable complete responses in heavily pretreated FL, with manageable toxicity profiles. CAR T-cell therapy (axicabtagene ciloleucel, lisocabtagene maraleucel, and tisagenlecleucel) are approved in R/R FL after two or more prior lines, offering high response rates albeit notable logistal and safety considerations. Frontline trials incorporating lenalidomide-rituximab have established chemotherapy-free option with long-term outcomes comparable to chemoimmunotherapy. Emerging data on antibody-drug conjugates and bispecific antibody combination therapy continue to expand the therapeutic arsenal. Despite favorable long-term outcomes for many patients with FL, relapse remains common and remission typically shortens with successive lines of therapy. The growing number of effective agents with distinct mechanisms of action creates both opportunity and complexity. Evidence-based sequencing strategies that account for prior therapy exposure, patient fitness and mechanism-specific considerations are increasingly critical to maximizing outcomes across the disease trajectory.</p>","PeriodicalId":10861,"journal":{"name":"Current Oncology Reports","volume":"28 1","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148618643","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DNA Repair, Epigenetic Dysregulation, and Cytokine Network Crosstalk in Head and Neck Cancer: Emerging Therapeutic Opportunities and Clinical Trials.","authors":"Nistha Agarwal, Garima Sharma, Ashish Ranjan Sharma, Vinod Kumar Gupta, Yuyuan Guo, Abhimanyu Kumar Jha, Jin-Chul Kim","doi":"10.1007/s11912-026-01808-0","DOIUrl":"10.1007/s11912-026-01808-0","url":null,"abstract":"<p><strong>Purpose of review: </strong>Head and neck cancer (HNC) is characterized by profound genomic instability, therapeutic resistance, and suboptimal survival outcomes, particularly in advanced-stage disease. This review aims to critically examine the mechanistic interplay between DNA damage response (DDR) pathways, epigenetic dysregulation, and cytokine-driven inflammatory networks, and to evaluate their collective impact on HNC progression and therapeutic vulnerability.</p><p><strong>Recent findings: </strong>Recent studies have demonstrated that defects in DDR pathways contribute to genomic instability and activate cytosolic DNA sensing via the cGAS-STING pathway, leading to type I interferon production and modulation of the tumor microenvironment. In addition, epigenetic alterations influence DNA repair mechanisms and immune responses. Cytokine networks involving IL-6, TNF-α, and NF-κB/STAT3 signaling play a central role in tumor progression, immune evasion, and therapy resistance. Combination therapies, including PARP/ATR inhibitors with immune checkpoint blockade and cytokine-targeting agents, have shown promising results in preclinical and early clinical studies. The intricate crosstalk among DDR deficiency, epigenetic alterations, and inflammatory signaling constitutes a central axis in HNC pathobiology and therapeutic resistance. Targeting these interconnected pathways through rational combination strategies offers a promising avenue to enhance treatment efficacy and advance precision oncology. Continued integration of molecular profiling and biomarker-driven approaches will be essential to optimize patient stratification and improve clinical outcomes in HNC.</p>","PeriodicalId":10861,"journal":{"name":"Current Oncology Reports","volume":"28 1","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148590462","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From Symptom Control to Precision Supportive Oncology: Integrating Artificial Intelligence in Supportive Oncology for Gastrointestinal Cancers.","authors":"Arunkumar Krishnan, Mellar P Davis, Kunal C Kadakia","doi":"10.1007/s11912-026-01810-6","DOIUrl":"10.1007/s11912-026-01810-6","url":null,"abstract":"<p><strong>Purpose of review: </strong>Gastrointestinal (GI) cancers are among the most common malignancies worldwide and impose a substantial symptom burden from diagnosis through survivorship. Despite advances in systemic therapies and surgical approaches, patients continue to experience undertreated symptoms, psychosocial distress, financial toxicity, and fragmented supportive care. This review examines how artificial intelligence (AI) may help transform GI supportive oncology from a reactive, episodic model to a proactive, continuous, and personalized approach.</p><p><strong>Recent findings: </strong>AI applications in GI supportive oncology are advancing along two related domains: (1) AI-enabled patient-reported outcome (PRO) tools, including real-time symptom monitoring, unsupervised symptom clustering, and AI-enhanced triage pathways; and (2) tumor-aware supportive care, including AI-driven radiomics for sarcopenia detection and multimodal prognostic models that inform supportive care needs. Systematic electronic PRO monitoring has been associated with improved survival and reduced acute care utilization, while AI-automated CT sarcopenia detection identifies muscle wasting that routine clinical documentation often misses. Important implementation challenges remain, including the black-box problem, algorithmic bias, privacy concerns, the digital divide, and regulatory uncertainty. Precision supportive oncology, integrating PRO-based symptom intelligence with imaging-derived risk stratification, has the potential to improve GI cancer care by making it more anticipatory and patient-centered. This review proposes a two-lane framework consisting of PRO-driven symptom intelligence and tumor-aware supportive care, unified by principles of privacy, explainability, and equity. Responsible adoption will require prospective validation, equitable design, and clinically interpretable systems.</p>","PeriodicalId":10861,"journal":{"name":"Current Oncology Reports","volume":"28 1","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148445021","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Infectious Complications of Antibody-Drug Conjugates: A Review of Safety Data from FDA-Approved Agents.","authors":"Georgios Schinas, Pantazis-Michael Voutsinas, Dimitra Stefanou, Christos Stafylidis, Aikaterini Gkoufa, Dimitrios C Ziogas, Panagiotis T Diamantopoulos, Helen Gogas, Amalia Anastasopoulou","doi":"10.1007/s11912-026-01804-4","DOIUrl":"10.1007/s11912-026-01804-4","url":null,"abstract":"<p><strong>Purpose of review: </strong>With fifteen agents now FDA-approved and indications expanding into earlier treatment lines, antibody-drug conjugates (ADCs) represent a rapidly growing class of targeted cancer therapeutics. Despite their selective mechanism of action, infectious complications are clinically significant and have been flagged as a disproportionate safety signal in post-marketing surveillance. This review characterizes the infection risk profiles of all fifteen FDA-approved ADCs through systematic extraction of prescribing information and pivotal trial safety data, and examines the pathophysiological mechanisms, antigen-specific clinical patterns, and evidence-based prophylaxis strategies applicable to this class.</p><p><strong>Recent findings: </strong>Calicheamicin-based agents carry the highest infection burden, with grade ≥ 3 infection rates exceeding 30-47% and near-universal severe neutropenia. CD30- and CD79b-targeting vedotin conjugates are associated with opportunistic infections-including progressive multifocal leukoencephalopathy and Pneumocystis jirovecii pneumonia-through mechanisms beyond myelosuppression, particularly T-cell immune surveillance disruption and bystander-effect lymphotoxicity. Solid tumor ADCs demonstrate lower overall infection rates with distinct organ-specific patterns: genitourinary infections predominate with Nectin-4- and Tissue Factor-directed agents, whereas pulmonary events characterize HER2- and c-Met-targeted conjugates. Linker cleavability, drug-to-antibody ratio, and payload metabolism are identified as key pharmacological determinants of myelosuppressive and infectious risk. Infectious complications of ADC therapy are clinically significant but heterogeneous, with risk profiles primarily determined by target antigen, immunologic context, and concurrent treatment. These findings support the growing adoption of a combined prevention strategy incorporating disease-based risk stratification and drug-directed infection prophylaxis.</p>","PeriodicalId":10861,"journal":{"name":"Current Oncology Reports","volume":"28 1","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13354691/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148419487","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Next-Generation Checkpoint Combinations: Optimizing PD-(L)1-Based Therapy Across the Advanced, Adjuvant, and Neoadjuvant Settings.","authors":"Fausto Petrelli, Lara Colombo Zefinetti, Andrea D'Alessio, Lorenzo Dottorini, Antonio Ghidini","doi":"10.1007/s11912-026-01809-z","DOIUrl":"10.1007/s11912-026-01809-z","url":null,"abstract":"<p><strong>Purpose of review: </strong>Programmed cell death 1 (PD-1) and programmed death ligand 1 (PD-L1) inhibitors are foundational components of therapy across many solid tumors, yet primary and acquired resistance limit durable benefit for a substantial proportion of patients. Rather than attempting a broad survey of every disease area, this review deliberately focuses on three tumor types in which PD-(L)1-based combinations have generated the most mature, practice-relevant evidence and in which the field is evolving most rapidly: renal cell carcinoma (RCC), urothelial (bladder) cancer, and non-small cell lung cancer (NSCLC). For each, we examine how combinations are being developed and positioned across the advanced, adjuvant, and neoadjuvant/perioperative settings, and we place selected cross-cutting strategies (dual checkpoint blockade, antibody-drug conjugates, hypoxia-inducible factor [HIF]-2α inhibition, and other partners) in that disease-specific context.</p><p><strong>Recent findings: </strong>In RCC, immune checkpoint inhibitor (ICI) plus vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor (TKI) doublets are established first-line standards, adjuvant pembrolizumab is the first agent to improve both disease-free and overall survival after nephrectomy, and the HIF-2α inhibitor belzutifan has become a post-ICI/TKI option while being tested earlier in disease. In bladder cancer, the antibody-drug conjugate enfortumab vedotin combined with pembrolizumab has displaced platinum chemotherapy as first-line therapy for advanced disease, and perioperative durvalumab added to neoadjuvant chemotherapy improves event-free and overall survival in muscle-invasive disease. In NSCLC, neoadjuvant and perioperative chemoimmunotherapy regimens now demonstrate overall survival benefit, complementing established advanced-disease and adjuvant strategies. We also summarize combinations that have failed-most notably concurrent PD-(L)1 blockade with EGFR or ALK TKIs in oncogene-driven NSCLC, and anti-TIGIT antibodies in phase III-because these negative results are as instructive as the successes. Within RCC, bladder cancer, and NSCLC, next-generation PD-(L)1 combinations are reshaping treatment across all disease stages. The magnitude of benefit, the relevant biomarkers, and the toxicity trade-offs differ substantially by tumor type and by setting. Successful development depends on a sound biologic rationale, biomarker-informed patient selection, and careful toxicity management, and the evidence base remains uneven-ranging from mature phase III data to early signals-which we make explicit throughout.</p>","PeriodicalId":10861,"journal":{"name":"Current Oncology Reports","volume":"28 1","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148390184","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}