MedComm – Oncology最新文献

{"title":"Separating Tobacco Exposure From Ancestry in East Asian and Western Lung Adenocarcinoma","authors":"Lv Liu, Rong Yu, Gao-Hui Cao, Ruo-Nan Li, Yi Dong, Hao Yan, Yu-Jie Jiang, Liang-Liang Fan, Shuai Guo","doi":"10.1002/mog2.70104","DOIUrl":"https://doi.org/10.1002/mog2.70104","url":null,"abstract":"<p>Lung adenocarcinoma (LUAD) shows different genomic profiles in East Asian (EAS) and Western populations, but smoking is unevenly distributed between these groups and may account for part of this contrast. Across our in-house cohort and five published whole-exome sequencing cohorts [<span>1-5</span>], 32.3% of EAS patients and 71.3% of Western patients were ever-smokers (Figure 1A; Supporting Information S1: Table S1). We therefore curated 1453 LUAD exomes and compared the two population groups separately among never-smokers and ever-smokers, with cohort-specific and pairwise analyses used to assess potential cohort effects. Three main findings emerged. First, EAS ever-smokers had genomic profiles similar to Western never-smokers: none of the tested differences in tumor mutation burden (TMB), core driver-mutation frequencies, or mutational signatures remained significant after multiple-testing correction. Second, accounting for smoking greatly narrowed the apparent ancestry signal. Of 2063 genes that differed in the pooled comparison, only 13 differed in both smoking groups, with <i>EGFR</i> and <i>KRAS</i> the only established LUAD drivers among them. Third, smoking-associated changes in SBS1 and SBS4 differed between the groups.</p><p>Western never-smokers had TMB and driver-mutation profiles resembled those of EAS ever-smokers (Figure 1A,B, top). Median TMB was 2.18 mutations/Mb in Western never-smokers (<i>n</i> = 239) and 2.39 mutations/Mb in EAS ever-smokers (<i>n</i> = 190) (median difference = −0.20 mutations/Mb; adjusted <i>p</i> = 0.97), compared with 1.29 mutations/Mb in EAS never-smokers (<i>n</i> = 398). None of the 15 canonical LUAD driver genes differed significantly between Western never-smokers (<i>n</i> = 239) and EAS ever-smokers (<i>n</i> = 146) after multiple-testing correction. <i>KRAS</i> was mutated in 17.6% and 17.8% of these two groups, respectively (OR for EAS ever-smokers vs. Western never-smokers = 1.02, 95% CI 0.60–1.75; adjusted <i>p</i> = 1.00), compared with 4.3% of EAS never-smokers. <i>KEAP1</i> showed a similar pattern, occurring in 13.4% of Western never-smokers and 10.3% of EAS ever-smokers (OR = 0.75, 95% CI 0.40–1.43; adjusted <i>p</i> = 1.00), but in only 0.7% of EAS never-smokers. The <i>KRAS</i> and <i>KEAP1</i> patterns were directionally consistent when TCGA and TRACERx were analyzed separately (Figure 1D, right). These findings caution against assumption that never-smokers provide a comparable genomic baseline across population groups.</p><p>Accounting for smoking sharply narrowed the somatic mutation differences between EAS and Western tumors (Figure 1B, bottom). In the pooled comparison, 2063 of 8428 genes differed between the two groups, whereas only 13 were significant in both the never-smoker and ever-smoker comparisons. Among these 13 genes, <i>EGFR</i> and <i>KRAS</i> were the only established LUAD drivers; the other 11 included long frequently mutated genes such as <i>TTN</i>, <i>MUC16</i> a","PeriodicalId":100902,"journal":{"name":"MedComm – Oncology","volume":"5 4","pages":""},"PeriodicalIF":8.5,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mog2.70104","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149205829","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intratumoral CTLA-4 Blockade: Decoupling Local Immune Remodeling From Systemic Toxicity","authors":"Luyan Chen, Mengke Niu, Haidong Cui, Zhijun Dai, Ming Yi","doi":"10.1002/mog2.70101","DOIUrl":"https://doi.org/10.1002/mog2.70101","url":null,"abstract":"<p>In the randomized phase 1b NIVIPIT trial, Tselikas et al. showed that low-dose intratumoral ipilimumab combined with intravenous nivolumab markedly reduced severe treatment-related adverse events while maintaining considerable antitumor activity [<span>1</span>]. These findings support intratumoral CTLA-4 blockade as a strategy to dissociate local immune activation from systemic toxicity and provide a conceptual framework for spatially restricted immunotherapy.</p><p>Increasing evidence suggests that the efficacy of anti-CTLA-4 therapy depends not only on checkpoint blockade itself but also on FcγR-mediated immune remodeling within the tumor microenvironment [<span>2</span>]. Unlike anti-PD-1 antibodies, whose efficacy largely depends on receptor occupancy and reinvigoration of exhausted T cells, ipilimumab is an Fc-competent IgG1 antibody capable of engaging Fcγ receptors and mediating depletion of intratumoral regulatory T (Treg) cells [<span>3</span>]. Therefore, intratumoral delivery may preserve the key effector mechanisms of anti-CTLA-4 therapy at the tumor site while reducing systemic exposure and peripheral immune activation. However, because murine and human FcγR systems differ, the contribution of individual FcγR subtypes requires validation in human tumors.</p><p>The NIVIPIT trial supports this concept by showing that substantial antitumor activity can be achieved in injected lesions despite markedly reduced circulating ipilimumab levels. This finding further suggests that CTLA-4 blockade is highly dependent on spatial immune context. Its efficacy may be shaped by localized interactions among activated Treg cells, FcγR-expressing macrophages, antigen-presenting cells, and tumor-reactive T cells [<span>4</span>]. In this setting, the injected lesion is not merely a drug delivery site, but may function as an immune-remodeling niche whose cellular composition determines both local tumor regression and the extent of systemic immune mobilization (Figure 1).</p><p>However, the study also highlights an important conceptual distinction between local immune remodeling and systemic immune priming. Although injected lesions responded strongly, responses in uninjected lesions were less pronounced, and systemic pharmacodynamic activation appeared attenuated compared with intravenous ipilimumab. Peripheral immune activation and inflammatory cytokine induction were also weaker in the intratumoral treatment arm. These findings suggest that intratumoral CTLA-4 blockade may effectively remodel the injected tumor microenvironment but may not fully reproduce the systemic immune amplification induced by conventional intravenous CTLA-4 blockade. Therefore, the apparent safety advantage of intratumoral therapy may partly reflect the same biological constraint that limits its ability to drive broad systemic antitumor immunity.</p><p>This distinction may have important translational implications. Systemic anti-CTLA-4 therapy likely exerts at least two parti","PeriodicalId":100902,"journal":{"name":"MedComm – Oncology","volume":"5 4","pages":""},"PeriodicalIF":8.5,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mog2.70101","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149146155","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cross-Modal Artificial Intelligence Integrating Dynamic MRI and Clinical Data for Breast Cancer Diagnosis and Nodal Metastasis Prediction","authors":"Wei Ren,&nbsp;Zifan He,&nbsp;Zhixian Deng,&nbsp;Zhenjun Huang,&nbsp;Gengxi Cai,&nbsp;Xiaohua Ban,&nbsp;Qiugen Hu,&nbsp;Zebang Zhang,&nbsp;Luhui Mao,&nbsp;Yujie Tan,&nbsp;Qing Peng,&nbsp;Zehua Wang,&nbsp;Ruichong Lin,&nbsp;Xian Yang,&nbsp;Xiaohui Duan,&nbsp;Herui Yao,&nbsp;Yunfang Yu","doi":"10.1002/mog2.70100","DOIUrl":"https://doi.org/10.1002/mog2.70100","url":null,"abstract":"<p>Accurate preoperative assessment of breast lesion malignancy and axillary lymph node (ALN) status is important for individualized breast cancer management, yet current approaches are limited by diagnostic variability and invasive nodal staging. We aimed to develop and validate a multicenter artificial intelligence framework for breast lesion classification and ALN metastasis prediction using dynamic contrast-enhanced magnetic resonance imaging (MRI) and preoperative clinical information. In this multicenter study, 3320 patients from four hospitals were assigned to a training cohort, an internal testing cohort, and two independent external validation cohorts. Lesion classification was based on MRI alone, whereas ALN prediction additionally incorporated clinical characteristics. MRI sequences were analyzed using a Video Swin Transformer Tiny backbone with low-rank adaptation and attention-based multiple-instance learning, with gated multimodal fusion used for ALN prediction. The model achieved AUCs of 1.000, 1.000, 1.000, and 0.994 for lesion classification and 0.991, 0.974, 0.987, and 0.960 for ALN prediction across the four cohorts. Calibration and decision curve analyses further characterized model performance, while exploratory survival analysis showed that AI-predicted ALN status was associated with disease-free survival. These findings support the potential of AI-assisted breast MRI to provide quantitative information for breast lesion characterization and preoperative assessment of ALN involvement.</p>","PeriodicalId":100902,"journal":{"name":"MedComm – Oncology","volume":"5 4","pages":""},"PeriodicalIF":8.5,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mog2.70100","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149146016","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Elranatamab Combined With Radiotherapy for Extramedullary Relapse Involving the Skull Base in Triple-Class Refractory Multiple Myeloma: A Case Report","authors":"Lu Zhou,&nbsp;Jingshu Meng,&nbsp;Qiaoyun Tan,&nbsp;Tao Liu,&nbsp;Xinxiu Liu,&nbsp;Fang Zhu,&nbsp;Liling Zhang","doi":"10.1002/mog2.70099","DOIUrl":"https://doi.org/10.1002/mog2.70099","url":null,"abstract":"&lt;p&gt;Multiple myeloma (MM) is a clonal plasma cell malignancy characterized by the proliferation of malignant plasma cells. Extramedullary disease (EMD), defined as plasma cell infiltration outside the bone marrow, represents an aggressive manifestation of MM. Neurological complications may occur when EMD involves the skull base or parasellar region, leading to cranial nerve dysfunction or visual impairment due to local mass effect. Treatment of EMD remains challenging, with limited effective therapeutic options.&lt;/p&gt;&lt;p&gt;BCMA-directed bispecific antibodies (BsAbs), including teclistamab, elranatamab, and linvoseltamab, represent a novel treatment strategy for relapsed or refractory multiple myeloma (RRMM), redirecting cytotoxic T cells to eliminate malignant plasma cells. Elranatamab, a BsAb targeting BCMA and CD3, achieved an objective response rate (ORR) of 61.0% in patients with RRMM. However, its single-agent efficacy was limited in patients with EMD, with an ORR of 38.5% versus 71.4% in those without EMD [&lt;span&gt;1&lt;/span&gt;]. Radiotherapy (RT) is an effective local treatment for EMD, providing rapid symptom relief and local disease control. The activity of elranatamab against EMD, particularly combined with RT, is undocumented. Here we describe a 60-year-old woman with triple-class refractory MM who developed EMD involving the skull base with soft tissue masses in the sellar region and dura mater. Treatment with elranatamab combined with RT resulted in rapid symptom improvement and tumor remission. This case suggests that combined systemic T-cell engagers and local RT may have complementary therapeutic efficacy in EMD.&lt;/p&gt;&lt;p&gt;A 60-year-old female patient presented in August 2022 with high-risk IgG lambda-type MM, characterized by elevated beta-2-microglobulin, 1q21 gain, and del(13q). She was staged as Durie-Salmon stage Ⅲ and International Staging System (ISS) stage Ⅲ. The clinical course is summarized in Figure 1A. Induction therapy comprising a planned six-cycle regimen of daratumumab, bortezomib, lenalidomide, and dexamethasone (D-VRD) commenced in September 2022, yielding a complete response (CR) by the conclusion of the fourth cycle. Subsequent therapy transitioned to daratumumab-lenalidomide-dexamethasone (DRd) maintenance for 19 months, followed by 3 months of lenalidomide maintenance. In January 2025, the patient experienced disease progression (PD) and received three cycles of carfilzomib, pomalidomide, and dexamethasone (KPd).&lt;/p&gt;&lt;p&gt;In April 2025, the patient developed left ptosis and vision loss. Magnetic resonance imaging (MRI) demonstrated suprasellar/parasellar lesions invading the sphenoid sinus (Figure 1B, left) and a left parietal dural mass measuring 27 × 7 mm (Figure 1C, left), supporting EMD with skull-base and dural involvement. Serologically free lambda light chain levels had risen from 198.37 to 388.45 mg/L with a κ/λ ratio of 0.028.&lt;/p&gt;&lt;p&gt;The patient received third-line therapy with elranatamab, initiated in May 2025 using st","PeriodicalId":100902,"journal":{"name":"MedComm – Oncology","volume":"5 3","pages":""},"PeriodicalIF":8.5,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mog2.70099","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149048082","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association Between BMI and the Efficacy and Safety of CDK4/6 Inhibitors in HR+/HER2− Advanced Breast Cancer: A Multicenter Retrospective Propensity Score Matched Cohort Study (CAMELIA)","authors":"Min Tian,&nbsp;Yijia Hua,&nbsp;Qian Liu,&nbsp;Nan Jin,&nbsp;Xinyu Wu,&nbsp;Kun Wang,&nbsp;Min Yan,&nbsp;Tao Sun,&nbsp;Chunfang Hao,&nbsp;Yanxia Zhao,&nbsp;Wei Li,&nbsp;Xiang Huang,&nbsp;Yongmei Yin","doi":"10.1002/mog2.70096","DOIUrl":"https://doi.org/10.1002/mog2.70096","url":null,"abstract":"<p>The prognostic value of body mass index (BMI) in hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2−) advanced breast cancer treated with CDK4/6 inhibitors remains unclear. We evaluated the association of baseline BMI with efficacy and safety outcomes in a multicenter retrospective real-world cohort of 588 patients. Propensity score matching (1:3) was used to balance baseline characteristics between patients with BMI ≥ 25 kg/m² and BMI &lt; 25 kg/m². Survival was assessed using Kaplan–Meier and Cox regression analyses, with sensitivity analyses using BMI cutoffs of 23 and 24 kg/m². After matching, 113 patients with BMI ≥ 25 kg/m² and 339 with BMI &lt; 25 kg/m² were analyzed. With a median follow-up of 21.5 months, BMI ≥ 25 kg/m² was associated with longer progression-free survival (PFS, 16.77 vs. 12.93 months; HR 0.737, 95% CI 0.554–0.981; <i>p</i> = 0.036), which remained significant after multivariable adjustment (HR 0.705; <i>p</i> = 0.021). Sensitivity analyses confirmed consistent PFS results across BMI thresholds. No differences were observed in overall survival (OS) or objective response rate (ORR). Adverse event profiles were comparable between groups. BMI ≥ 25 kg/m² was independently associated with improved PFS, supporting that BMI may have prognostic relevance in this population.</p>","PeriodicalId":100902,"journal":{"name":"MedComm – Oncology","volume":"5 4","pages":""},"PeriodicalIF":8.5,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mog2.70096","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149029022","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LIPE-AS1 Facilitates Prostate Cancer Progression via Suppressing Cuproptosis Through the miR-330-3p/MGAT5 Axis","authors":"Qiang Shen,&nbsp;Qu Leng,&nbsp;Kaihui Wu,&nbsp;Guorui Li,&nbsp;Yiyou Mao,&nbsp;Jun Wu,&nbsp;Ziyi Song,&nbsp;Zhihai Deng,&nbsp;Hangyang Peng,&nbsp;Jun Zou,&nbsp;Jiamin Wang,&nbsp;Ping Liu,&nbsp;Zihao Zou,&nbsp;Zhaojun Pan,&nbsp;Jianfeng Zhong,&nbsp;Yubin Li,&nbsp;Nan Deng,&nbsp;Xiangming Mao,&nbsp;Daojun Lv","doi":"10.1002/mog2.70098","DOIUrl":"https://doi.org/10.1002/mog2.70098","url":null,"abstract":"<p>Cuproptosis, a copper-dependent form of regulated cell death, represents a potential metabolic vulnerability in cancer. However, the upstream regulators of this process in prostate cancer (PCa) remain unclear. This study identified long noncoding RNA (lncRNA) LIPE-AS1 as a key suppressor of cuproptosis in PCa. Elevated levels of LIPE-AS1 were observed in PCa, which inversely correlated with the core cuproptosis gene ferredoxin 1 (<i>FDX1</i>). Silencing LIPE-AS1 sensitized cells to the cuproptosis inducer elesclomol-Cu (Ele-Cu), an effect that was reversible through copper chelation. Mechanistically, cytoplasmic LIPE-AS1 functioned as a competing endogenous RNA (ceRNA) by sponging miR-330-3p, thereby derepressing its target <i>MGAT5</i>. MGAT5 subsequently modulated the expression of cuproptosis-associated proteins FDX1, dihydrolipoamide <i>S</i>-acetyltransferase (DLAT), and dihydrolipoamide <i>S</i>-succinyltransferase (DLST). Rescue experiments demonstrated that MGAT5 overexpression (MGAT5-OE) reversed the cuproptosis sensitivity induced by LIPE-AS1 knockdown. In vivo studies revealed that LIPE-AS1 depletion synergized with elesclomol to suppress tumor growth. Collectively, the LIPE-AS1/miR-330-3p/MGAT5 axis is defined as a critical pathway restraining cuproptosis in PCa, providing a mechanistic basis for targeting this circuit to overcome therapy resistance.</p>","PeriodicalId":100902,"journal":{"name":"MedComm – Oncology","volume":"5 3","pages":""},"PeriodicalIF":8.5,"publicationDate":"2026-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mog2.70098","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149047845","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Carbon Dots in Breast Cancer Theranostics: Structure–Property Relationships, Mechanisms, and Translational Insights","authors":"Srija Sur,&nbsp;Pegah Varamini","doi":"10.1002/mog2.70095","DOIUrl":"https://doi.org/10.1002/mog2.70095","url":null,"abstract":"<p>Carbon dots (C-dots) are an emerging class of carbon-based nanomaterials that combine exceptional optical properties, tuneable surface chemistry, and biocompatibility, making them promising platforms for cancer theranostics. In breast cancer management, C-dots have been investigated for integrated diagnostic and therapeutic functions, including fluorescence imaging, targeted drug delivery, photodynamic therapy (PDT), and photothermal therapy (PTT). This review summarises recent advances in C-dot synthesis methods—covering both top-down and bottom-up strategies—with emphasis on how synthesis parameters and surface engineering influence optical performance, targeting specificity, and therapeutic efficacy. The structure–property relationships of C-dots are critically examined in the context of breast cancer models, highlighting the roles of particle size, doping, functionalisation, and charge in modulating biodistribution and treatment outcomes. Mechanistic insights into C-dot-mediated PDT, PTT, and drug delivery are provided, alongside discussion of in vitro and in vivo evaluations. The challenges of long-term toxicity assessment, large-scale synthesis, and clinical translation are analysed, and future research opportunities are proposed, including stimuli-responsive systems, hybrid nanostructures, and manufacturing pathways compliant with good manufacturing practice (GMP). By focusing on materials design principles and their biological implications, this review aims to guide the rational development of next-generation C-dots for effective and safe breast cancer theranostics.</p>","PeriodicalId":100902,"journal":{"name":"MedComm – Oncology","volume":"5 3","pages":""},"PeriodicalIF":8.5,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mog2.70095","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148942757","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrative Multi-Omics Profiling Reveals Age-Associated Genomic and Tumor Microenvironmental Heterogeneity in Colorectal Cancer","authors":"Yang Guo,&nbsp;Yajiao He,&nbsp;Tao Zhou,&nbsp;Haidong Zhang,&nbsp;Fei Liao,&nbsp;Yuelan Wang,&nbsp;Hai-Ning Chen,&nbsp;Li-Bin Huang,&nbsp;Xuyang Xia,&nbsp;Yiqi Deng,&nbsp;Jing Wu,&nbsp;Siyu Yang,&nbsp;Heng Xu,&nbsp;Zong-Guang Zhou,&nbsp;Yang Shu,&nbsp;Lie Yang","doi":"10.1002/mog2.70094","DOIUrl":"https://doi.org/10.1002/mog2.70094","url":null,"abstract":"<p>Early-onset colorectal cancer (EOCRC) is increasing worldwide, yet the molecular basis underlying its age-related heterogeneity remains insufficiently defined. To address this gap, we performed whole-exome sequencing in a Chinese EOCRC cohort diagnosed before 40 years of age (<i>n</i> = 111), bulk transcriptome sequencing in a subset of these tumors (<i>n</i> = 59), and whole-exome sequencing in an independent Chinese colorectal cancer cohort spanning a broader age range (<i>n</i> = 210). We then integrated these data with publicly available somatic mutation, bulk RNA-seq, and single-cell transcriptomic datasets to characterize age-associated tumor-intrinsic and microenvironmental features. Genomic analyses revealed a distinct EOCRC landscape, including lower frequencies of <i>APC</i> and <i>KRAS</i> mutations, more frequent <i>SMAD4</i> disruption through mutation or copy-number loss, and enrichment of the <i>PTPRK-RSPO3</i> fusion. Single-cell analyses further showed increased infiltration of CD4⁺ memory T cells and mast cells in EOCRC, whereas later-onset colorectal cancer was characterized by SPP1⁺ macrophage predominance and a strengthened interaction axis between FAP⁺ cancer-associated fibroblasts and SPP1⁺ macrophages. Therapeutic evaluation in aged mouse models, together with single-cell analysis of immunotherapy-treated patients, indicated reduced PD-1 blockade efficacy with increasing age. Together, these findings support age-informed molecular classification and therapeutic stratification in colorectal cancer.</p>","PeriodicalId":100902,"journal":{"name":"MedComm – Oncology","volume":"5 3","pages":""},"PeriodicalIF":8.5,"publicationDate":"2026-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mog2.70094","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148942818","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterization of 3′-Terminal 2′-O-Methylation miRNAs as Diagnostic Biomarkers for Colorectal Cancer","authors":"Yanting Wei,&nbsp;Yuan Fang,&nbsp;Xi Chen,&nbsp;Hongyuan Guo,&nbsp;Xu Guo","doi":"10.1002/mog2.70091","DOIUrl":"https://doi.org/10.1002/mog2.70091","url":null,"abstract":"&lt;p&gt;While 3′-terminal 2′-&lt;i&gt;O&lt;/i&gt;-methylation (3′t-2′ Ome) of microRNAs (miRNAs) was primarily documented in plants and insects, our group recently identified these modifications in mammalian tumors and demonstrated their diagnostic potential in non-small cell lung cancer (NSCLC) [&lt;span&gt;1, 2&lt;/span&gt;]. Crucially, unlike traditional unmethylated miRNAs, measurement of 3′t-2′ Ome provides robust, self-normalizing quantification without relying on unstable reference genes in liquid biopsies. Here, we systematically evaluated plasma 3′t-2′ Ome miRNA profiles and identified a highly accurate 3-miRNA panel (Let-7f-5p, miR-100-5p, and miR-200b-3p) for colorectal cancer (CRC). This noninvasive biomarker panel demonstrates exceptional diagnostic efficacy, significantly outperforming conventional clinical markers and offering a highly translational tool for CRC screening.&lt;/p&gt;&lt;p&gt;Using sequential screening, training, and validation phases, we evaluated 128 CRC patients and 123 controls for plasma 3′t-2′ Ome candidates. Participant demographics and clinical characteristics are detailed in Table S1. Statistical analysis revealed no significant differences between groups in age (&lt;i&gt;p&lt;/i&gt; = 0.108) and gender (&lt;i&gt;p&lt;/i&gt; = 0.939). Blood samples from CRC patients were collected before surgery, chemotherapy, or radiotherapy, thereby reducing potential treatment-related influences on circulating miRNA profiles.&lt;/p&gt;&lt;p&gt;As established previously, 3′t-2′ Ome modifications impair adapter ligation efficiency, introducing sequencing bias [&lt;span&gt;1&lt;/span&gt;]. We therefore applied sodium periodate (NaIO&lt;sub&gt;4&lt;/sub&gt;) treatment, which removes oxidation-sensitive small RNAs but retains terminally methylated species. Coupling this enrichment step with small RNA deep sequencing allowed us to profile miRNAs with differential methylation in CRC plasma. The oxidation efficiency is summarized in Figure S1.&lt;/p&gt;&lt;p&gt;Most mammalian miRNAs lost signal after oxidation, consistent with an unmethylated 3′ terminus. By contrast, a subset detected in CRC plasma remained stable after periodate exposure (Figure 1A). These data suggested that a subset of circulating miRNAs may acquire disease-associated terminal methylation and warranted further validation using targeted reverse transcription quantitative polymerase chain reaction (RT-qPCR) assays.&lt;/p&gt;&lt;p&gt;To validate these findings, we preliminarily screened 17 candidate miRNAs using stem-loop and poly(A)-tailing RT-qPCR [&lt;span&gt;3&lt;/span&gt;] with plasma from 10 CRC patients and 10 healthy controls selected from the screening cohort. In this assay, ΔCT was calculated as CT&lt;sub&gt;tailing&lt;/sub&gt; − CT&lt;sub&gt;stemloop&lt;/sub&gt;, reflecting the relative 3′t-2′ Ome level of each miRNA. Because both reactions measure the same miRNA from the same RNA preparation, this paired design largely cancels out differences in RNA input, extraction efficiency, and total miRNA abundance. It therefore avoids the uncertainty associated with circulating miRNA reference genes, which are often u","PeriodicalId":100902,"journal":{"name":"MedComm – Oncology","volume":"5 3","pages":""},"PeriodicalIF":8.5,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mog2.70091","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148942543","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immune Checkpoint Inhibitors in Cancer Therapy: Clinical Landscape, Resistance Mechanisms, and Therapeutic Innovations","authors":"Qiongyu Zhang,&nbsp;Zhi Qin,&nbsp;Caijuan Guo","doi":"10.1002/mog2.70097","DOIUrl":"https://doi.org/10.1002/mog2.70097","url":null,"abstract":"<p>Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of solid tumors, yet only a limited subset of patients achieves durable disease control. While China has emerged as a major contributor to global ICI development, a comprehensive synthesis of recent trial data and resistance mechanisms is urgently needed to guide clinical practice. This review examines the evolving landscape of ICI-based combination therapies, including regimens that combine ICI with chemotherapy, targeted therapy, antibody–drug conjugates, antiangiogenic agents, and radiotherapy, which have expanded first-line treatment options across multiple solid tumors and, in selected settings, have improved disease control or survival beyond historical monotherapy benchmarks. An in-depth analysis of the molecular mechanisms underlying primary and acquired resistance to ICIs is then provided, drawing on recent advances in multiomics. Building on this framework, emerging, mechanism-matched strategies designed to overcome specific resistance nodes are critically evaluated. Finally, the promise of integrating spatial transcriptomics and artificial intelligence to help shift ICI therapy from empirical combination toward mechanism-guided precision immuno-oncology is discussed. By bridging the gap between clinical evidence and molecular insights, this review offers a perspective that may help accelerate the rational design of next-generation ICI-based strategies and improve patient outcomes.</p>","PeriodicalId":100902,"journal":{"name":"MedComm – Oncology","volume":"5 3","pages":""},"PeriodicalIF":8.5,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mog2.70097","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148942040","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}