Journal of the National Cancer Center最新文献

{"title":"Neoantigen identification and TCR-T therapy development for solid tumors: current advances and future perspectives","authors":"Xinyao Zheng,&nbsp;Yahui Zhao,&nbsp;Zhihua Liu","doi":"10.1016/j.jncc.2025.07.001","DOIUrl":"10.1016/j.jncc.2025.07.001","url":null,"abstract":"<div><div>Recently, T cells expressing engineered T cell receptor (TCR-T cells) have become recognized as a promising tumor cell therapy for solid tumors because of their ability to selectively kill tumor cells with less destruction of other cells and their high safety when used as autologous T cells. Several studies and clinical tests have been conducted to demonstrate its potential as a novel therapy. However, previous research has mainly focused on antigens; these common targets for TCR-T are tumor-associated antigens, which exhibit expression not only in tumor cells but also in normal cells, resulting in off-target risk and not considering the heterogeneity of different patients. In contrast, neoantigens offer superior specificity as they are uniquely expressed on tumor cells due to genomic alterations. Given the frequent occurrence and notable role of genetic mutations in tumorigenesis and tumor progression, identification and targeting of neoantigens is a valuable therapeutic direction. This perspective delves into various antigen classifications, including their characteristics and advantages, as well as strategies for identifying and validating neoantigens that have emerged from numerous research studies. These insights are crucial for guiding the search for new neoantigens. We also review significant and representative studies involving TCR-T and other immunotherapies that target neoantigens to assess the therapeutic effectiveness of TCR-T therapy. Moreover, we discuss the challenges and complexities inherent in TCR-T therapy and propose potential solutions for these issues. In this perspective, we aim to provide fresh perceptions and strategies for cancer treatment by highlighting the potential of TCR-T and exploring its challenges and future directions. It also seeks to propel the development of precision medicine and personalized therapy, offering hope for more effective and targeted cancer treatments in the future.</div></div>","PeriodicalId":73987,"journal":{"name":"Journal of the National Cancer Center","volume":"5 5","pages":"Pages 429-440"},"PeriodicalIF":9.4,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145189653","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcriptomic predictors of prostate cancer recurrence following focal cryotherapy: a pooled analysis of phase II trial and prospective cohort data","authors":"Kae Jack Tay ,&nbsp;Boon Hao Hong ,&nbsp;Enya Hui Wen Ong ,&nbsp;Kah Min Tan ,&nbsp;Gianella Cabuhat Pacho ,&nbsp;Samantha Jingxuan Wong ,&nbsp;Yu Guang Tan ,&nbsp;Yan Mee Law ,&nbsp;Nye Thane Ngo ,&nbsp;Puay Hoon Tan ,&nbsp;John S.P. Yuen ,&nbsp;Henry S.S. Ho ,&nbsp;Kenneth Chen ,&nbsp;Jiping Peng ,&nbsp;Clare Wei Tian Foo ,&nbsp;Xin Xiu Sam ,&nbsp;Jeffrey K.L. Tuan ,&nbsp;Ravindran Kanesvaran ,&nbsp;Rajan T. Gupta ,&nbsp;Steven Rozen ,&nbsp;Melvin Lee Kiang Chua","doi":"10.1016/j.jncc.2025.04.002","DOIUrl":"10.1016/j.jncc.2025.04.002","url":null,"abstract":"<div><h3>Objective</h3><div>Focal therapy (FT) is a potential treatment option for limited-volume clinically-significant prostate cancer (csPCa). However, despite rigorous selection, approximately 20% of patients experience early failure. We investigated the association of transcriptomic profiles and csPCa recurrence post-FT.</div></div><div><h3>Methods</h3><div>52 men from a phase II trial (NCT04138914) and a prospective observational cohort underwent focal cryotherapy for csPCa. Patients underwent multiparametric magnetic resonance imaging, and targeted and systematic-saturation biopsy before- and 1-year post-FT. Recurrence was defined as grade-group (GG) ≥2 cancer in the 1-year post-FT biopsy. Pre-treatment lesions were profiled using the Decipher genomic classifier (GC). GC scores, luminal-basal status, tumor microenvironment and cancer hallmark pathways were correlated with csPCa recurrence.</div></div><div><h3>Results</h3><div>Median PSA was 7.0 ng/dl; 37/52 (71.1%) men had GG2, 12/52 (23.1%) GG3, and 3/52 (5.8%) GG4 cancer. Recurrence was observed in 9/52 (17.3%) men. Median GC score was higher in patients with recurrence (0.60 <em>vs</em> 0.38, <em>P</em> = 0.014) and remained significantly associated with recurrence after adjustment for GG (adjusted <em>OR</em>: 1.37 [95% CI: 1.01–1.93], <em>P</em> = 0.04). Luminal-proliferative tumors based on the prostate cancer-specific subtyping classifier (PSC) had more csPCa recurrence compared with luminal-differentiated (LD) and basal subtypes (30.4% <em>vs</em> 0% [LD] <em>vs</em> 15.4% [basal-neuroendocrine] and 14.3% [basal-immune], <em>P</em> = 0.027). Higher expression of DNA repair pathway was also associated with recurrence (<em>OR</em>: 2.12 [95% CI: 1.09–4.57], <em>P</em> = 0.025).</div></div><div><h3>Conclusions</h3><div>Higher GC score is associated with risk of csPCa recurrence post-FT. Patients with GC low-risk and PSC-LD csPCa may represent the ideal subgroup for FT. Prospective validation in a large cohort is warranted.</div></div>","PeriodicalId":73987,"journal":{"name":"Journal of the National Cancer Center","volume":"5 5","pages":"Pages 515-523"},"PeriodicalIF":9.4,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145189649","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spatial and maturity heterogeneity of tertiary lymphoid structures shapes immune microenvironment and progression in prostate cancer","authors":"Zhongyuan Wang ,&nbsp;Qintao Ge ,&nbsp;Ren Mo ,&nbsp;Jiahe Lu ,&nbsp;Xi Tian ,&nbsp;Aihetaimujiang Anwaier ,&nbsp;Shiqi Ye ,&nbsp;Siqi Zhou ,&nbsp;Weihang Guo ,&nbsp;Chuanhai Cai ,&nbsp;Jianfeng Yang ,&nbsp;Hailiang Zhang ,&nbsp;Xiaojian Qin ,&nbsp;Dingwei Ye ,&nbsp;Wenhao Xu","doi":"10.1016/j.jncc.2025.06.003","DOIUrl":"10.1016/j.jncc.2025.06.003","url":null,"abstract":"<div><h3>Background</h3><div>Tertiary lymphoid structure (TLS), ectopic lymphoid aggregates formed in response to chronic inflammation, have emerged as potential prognostic biomarkers and mediators of anti-tumor immunity in various cancers. However, the heterogeneity of TLS spatial distribution, maturity, and their prognostic and immunological significance in prostate cancer (PCa) remain poorly characterized.</div></div><div><h3>Methods</h3><div>We utilized immunohistochemistry, multispectral fluorescence immunohistochemistry (mIHC) and spatial multi-omics analyses to evaluate the heterogeneity of TLS and its relationship with immune components in the tumor microenvironment (TME). Prognostic implications were assessed in 701 PCa patients from the TCGA and Fudan University Shanghai Cancer Center cohorts. The association between TLS heterogeneity and immunoreactivity was assessed through the quantification of immune cell infiltration. CellTreck and robust cell type decomposition deconvolution algorithms were used to decipher the colocalization features of each cell, cell-cell communication and ligand-receptor features within TLS regions.</div></div><div><h3>Results</h3><div>In PCa, TLSs were detected in approximately 20 % of patients across both cohorts, with intratumoral TLS (intra-TLS) being twice as prevalent as peritumoral TLS (peri‑TLS). Patients harboring intra-TLS exhibited significantly longer disease-free and progression-free survival. Compared to peri‑TLS, intra-TLS were more mature, characterized by increased T-effector cell infiltration, activation of interferon pathways, and the presence of follicular dendritic cell centers and B cell aggregates. Notably, compared with immature TLS, mature TLS were markedly associated with reduced PD-L1 expression, lower regulatory T cells (Tregs) infiltration, and increased high endothelial venules (HEVs) density, indicative of an immunologically active microenvironment. Spatial multi-omics analysis revealed that mature TLS exhibited enriched immune cell diversity and HEVs density, suggesting enhanced anti-tumor immunity. Furthermore, cell-cell communication analysis identified significant interactions between CCL5⁺ dendritic cells and ACKR1⁺ activated B cells within mature TLS, reflecting the enhanced capacity of mature TLS to orchestrate robust antigen presentation and B-cell-driven immune responses.</div></div><div><h3>Conclusions</h3><div>In conclusion, this study highlights the prognostic and immunological implications of TLS heterogeneity in PCa, demonstrating that the spatial distribution and maturity of TLSs are closely linked to TME activation and improved clinical outcomes. These findings provide novel insights into the immune landscape of PCa and establish a foundation for immune-based precision stratification and therapeutic development.</div></div>","PeriodicalId":73987,"journal":{"name":"Journal of the National Cancer Center","volume":"5 5","pages":"Pages 501-514"},"PeriodicalIF":9.4,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145189648","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Colorectal cancer screening in adults aged 45–49: provider availability, CT colonography access, and screening rates","authors":"Rachel Liu-Galvin ,&nbsp;Zhigang Xie ,&nbsp;Young-Rock Hong","doi":"10.1016/j.jncc.2025.03.003","DOIUrl":"10.1016/j.jncc.2025.03.003","url":null,"abstract":"<div><h3>Background</h3><div>The US Preventive Services Task Force updated its colorectal cancer (CRC) screening guidelines in 2021, recommending screening for adults aged 45–49. This study aimed to evaluate CRC screening prevalence among this newly eligible population and assess its association with healthcare provider supply and CT colonography facility availability in 2022.</div></div><div><h3>Methods</h3><div>Using 2022 Behavioral Risk Factor Surveillance System data (n = 25,592), we estimated CRC screening prevalence among adults aged 45–49 and the prevalence of different screening modalities across various sociodemographic factors. We examined associations between screening rates and state-level healthcare provider supply using 2021–2022 Area Health Resources File data. Spearman rank-order correlations assessed relationships between provider supply, CT colonography facility availability, and screening prevalence.</div></div><div><h3>Results</h3><div>Overall CRC screening prevalence was 34.5% (95% CI: 33.4%–35.8%). Endoscopic tests were most common (74.9%), followed by stool-based tests (9.3%) and CT colonography (0.5%). Significant variations in screening modalities were observed across sociodemographic factors. Gastroenterology physician supply positively correlated with overall CRC screening prevalence (ρ = 0.42, <em>P</em> = 0.002) and endoscopy screening prevalence (ρ = 0.38, <em>P</em> = 0.005). CT colonography facility availability weakly correlated with CT colonography screening prevalence (ρ = 0.15, <em>P</em> = 0.316), although this was not significant.</div></div><div><h3>Conclusions</h3><div>CRC screening rates among newly eligible adults aged 45–49 appear to be suboptimal in 2022. Disparities in screening methods across sociodemographic factors highlight potential access barriers, particularly for endoscopic tests. The association between gastroenterology physician supply and screening rates emphasizes the importance of addressing projected workforce shortages. Targeted efforts are needed to increase CRC screening uptake in this age group and ensure equitable access to screening services.</div></div>","PeriodicalId":73987,"journal":{"name":"Journal of the National Cancer Center","volume":"5 4","pages":"Pages 414-425"},"PeriodicalIF":9.4,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144723415","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Challenging go/no-go decision scenarios and design recommendations in phase II oncology trials","authors":"Dandan Kong ,&nbsp;Huilei Miao ,&nbsp;Xuejing Zhang ,&nbsp;Huiyao Huang ,&nbsp;Ning Li","doi":"10.1016/j.jncc.2025.06.002","DOIUrl":"10.1016/j.jncc.2025.06.002","url":null,"abstract":"","PeriodicalId":73987,"journal":{"name":"Journal of the National Cancer Center","volume":"5 4","pages":"Pages 357-361"},"PeriodicalIF":9.4,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144723495","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Decoding the tumor microenvironment: insights into immunotherapy and beyond","authors":"Wenhao Xu ,&nbsp;Jiahe Lu ,&nbsp;Hailiang Zhang ,&nbsp;Dingwei Ye","doi":"10.1016/j.jncc.2025.04.003","DOIUrl":"10.1016/j.jncc.2025.04.003","url":null,"abstract":"","PeriodicalId":73987,"journal":{"name":"Journal of the National Cancer Center","volume":"5 4","pages":"Pages 426-428"},"PeriodicalIF":9.4,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144723417","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real-world effectiveness of goserelin 10.8-mg compared to goserelin 3.6-mg in premenopausal and perimenopausal Chinese patients with hormone receptor positive breast cancer: a cohort study","authors":"Yongsheng Wang ,&nbsp;Xi Wang ,&nbsp;Jiong Wu ,&nbsp;Hong Liu ,&nbsp;Jiuda Zhao ,&nbsp;Jian Huang ,&nbsp;Jianxia Liu ,&nbsp;Youling Gong ,&nbsp;Hao Wang ,&nbsp;Huaqing Yang ,&nbsp;Guorong Zou ,&nbsp;Quchang Ouyang ,&nbsp;Guoqin Jiang ,&nbsp;Huijuan Liu ,&nbsp;Sujie Ni ,&nbsp;Binghe Xu ,&nbsp;Jinming Yu","doi":"10.1016/j.jncc.2025.02.006","DOIUrl":"10.1016/j.jncc.2025.02.006","url":null,"abstract":"<div><h3>Background</h3><div>Few studies compared the effectiveness of the 3-monthly goserelin 10.8-mg and the monthly 3.6-mg depot in inducing ovarian function suppression for premenopausal patients with hormone receptor positive (HR+) breast cancer. We conducted a large-scale real-world study (RWS) in China to validate the non-inferiority of goserelin 10.8-mg to the 3.6-mg depot.</div></div><div><h3>Methods</h3><div>This multicenter, retrospective-prospective, non-inferiority study compared goserelin 10.8-mg with 3.6-mg in suppressing estradiol (E2) levels in premenopausal and perimenopausal patients with HR+ breast cancer. Eligible patients were identified, and their demographic and clinical data were obtained from hospital medical records. The observation period was 28 weeks. Propensity score matching (PSM) ensured baseline comparability. The primary endpoint was the proportion of patients with E2 suppression to postmenopausal level at Week 12±4. Difference in proportions and 95 % CI was calculated by Newcombe-Wilson score method. The non-inferiority margin was -10 %. Subgroup and sensitivity analyses assessed result robustness.</div></div><div><h3>Results</h3><div>From 1st January, 2015 to 15th December, 2023, 15,629 patients from 16 hospitals nationwide were screened, with 1,060 eligible patients included in the full analysis set (3.6-mg group: 678; 10.8-mg group: 382). Post-PSM, the primary endpoint was analyzed in 590 patients (295 in each group). At Week 12±4, the proportion of patients with E2 suppression was 99.1 % (95 % CI: 96.9 %–99.8 %) for goserelin 10.8-mg and 95.3 % (95 % CI: 91.0 %–97.6 %) for goserelin 3.6-mg. The difference was 3.8 % (95 % CI: 0.6 %–8.1 %) with the lower limit of 95 % CI greater than the non-inferiority margin. All subgroup analyses, including those based on age (≤45 or &gt;45 years) and previous chemotherapy (yes/no), and all sensitivity analyses on the primary endpoint were consistent with the main analysis.</div></div><div><h3>Conclusions</h3><div>This RWS validated the non-inferiority of goserelin 10.8-mg 3-monthly to 3.6-mg monthly in Chinese patients with HR+ breast cancer, where high E2 suppression rates were achieved in both goserelin dosage groups.</div></div><div><h3>Trial registration</h3><div><span><span>ClinicalTrials.gov</span><svg><path></path></svg></span> (NCT05184257).</div></div>","PeriodicalId":73987,"journal":{"name":"Journal of the National Cancer Center","volume":"5 4","pages":"Pages 392-401"},"PeriodicalIF":9.4,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144723505","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of infraclavicular and supraclavicular lymph nodes in breast cancer patients receiving neoadjuvant chemotherapy: implications for regional lymph node classification","authors":"Yanyu Chen ,&nbsp;Yuzhi Song ,&nbsp;Zhonghua Han ,&nbsp;Hui Han ,&nbsp;Tianlan Tang ,&nbsp;Silin Chen ,&nbsp;Ruizhi Zhao ,&nbsp;Cheng Huang ,&nbsp;Guiqing Shi ,&nbsp;Yuping Lin ,&nbsp;Ying Wang ,&nbsp;Liuqing Jiang ,&nbsp;Jinhua Chen ,&nbsp;Chunsen Xu ,&nbsp;Fangmeng Fu ,&nbsp;Chuan Wang ,&nbsp;Yong Yang","doi":"10.1016/j.jncc.2025.02.005","DOIUrl":"10.1016/j.jncc.2025.02.005","url":null,"abstract":"<div><h3>Background</h3><div>Metastasis to the infraclavicular and supraclavicular lymph nodes (ISLNs) is an important factor that predicts poor survival in patients with breast cancer; however, pathological nodal staging does not traditionally include ISLNs because of their non-routine surgical dissection. This study aimed to evaluate the prognostic impact of ISLN metastasis and propose a refined nodal staging system tailored for patients undergoing neoadjuvant chemotherapy (NAC).</div></div><div><h3>Methods</h3><div>We retrospectively reviewed 1,072 patients with breast cancer with or without ISLN metastasis who received NAC at two institutions (Fujian cohort and Hebei cohort) from 2010 to 2022. We conducted detailed survival analysis to evaluate the diagnostic consistency and prognostic significance of ISLNs.</div></div><div><h3>Results</h3><div>There were no survival differences among patients with ISLN involvement across different assay methodologies and patient cohorts. Among 887 patients in the Fujian cohort, 238 patients (26.8 %) with positive ISLNs had significantly inferior 3-year progression-free survival (PFS, 75.9 % vs. 90.4 %, <em>P</em> &lt; 0.001) and overall survival (OS, 90.6 % vs. 95.9 %, <em>P</em> &lt; 0.001). After adjusting for potential confounders, ISLN involvement persisted as an independent predictor of both PFS and OS. We propose a refined axillary classification that combines pathological axillary staging post-NAC with ISLN involvement, revealing 3-year PFS rates of 95.3 %, 87.6 %, 73.4 %, and 64.5 % for the respective four groups defined by this refined classification combining axillary stage and ISLN status.</div></div><div><h3>Conclusions</h3><div>Involvement of the ISLNs was associated with a worse prognosis, underscoring their prognostic value. This finding highlights the potential of ISLN status to influence decisions regarding adjuvant treatment in patients with breast cancer.</div></div>","PeriodicalId":73987,"journal":{"name":"Journal of the National Cancer Center","volume":"5 4","pages":"Pages 402-413"},"PeriodicalIF":9.4,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144723416","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Silver Jubilee of HER2 targeting: a clinical success in breast cancer","authors":"Jianli Zhao ,&nbsp;Ziyue Zhou ,&nbsp;Phei Er Saw ,&nbsp;Erwei Song","doi":"10.1016/j.jncc.2024.12.008","DOIUrl":"10.1016/j.jncc.2024.12.008","url":null,"abstract":"<div><div>In the last century, scientists have discovered that when human epidermal growth factor receptor 2 (HER2) is overexpressed or amplified—found in approximately 15 %–20 % of breast cancer patients—it significantly increases the risk of tumor recurrence and metastasis. This crucial discovery has made anti-HER2 therapy a central focus in breast cancer research and treatment. HER2 protein overexpression, along with gene amplification or mutation, is commonly seen in breast cancer. Techniques like immunohistochemistry and fluorescence in situ hybridization are used to detect HER2 expression and amplification, categorizing tumors as having high, low, or no HER2 expression, and highlighting their heterogeneity. Monoclonal antibodies are well-established in treating breast cancers with a high HER2 expression, while antibody-drug conjugates have shown effectiveness in cases with a lower expression. Additionally, tyrosine kinase inhibitors and monoclonal antibodies optimized for antibody-dependent cellular cytotoxicity have expanded treatment options, allowing for effective therapies in breast cancers with lower HER2 expression levels. Even for tumors with HER2 mutations or low expressions, anti-HER2 therapies can still be effective. Newer treatments, like bispecific antibodies and vaccines, are being tested in clinical trials and are expected to play a significant role in treating breast cancers with different HER2 expression profiles. These advances have revolutionized neoadjuvant therapy, guiding postoperative and intensive treatment strategies based on how well the therapies work. However, challenges such as drug resistance, drug interactions, and the mechanisms of HER2-targeted therapies are closely linked to the tumor's immune microenvironment. As research continues, the complexity and diversity of HER2 as a target across various cancer types have become increasingly clear, presenting new challenges and driving innovation. Since the discovery of HER2 as a target, it has dramatically changed the landscape of breast cancer diagnosis, treatment, and prognosis. With more than two decades of development, the potential for further advances in HER2-targeted therapies continues to grow. This review aims to provide a comprehensive overview of current progress and future directions in HER2-targeted therapies for breast cancer and their clinical implications.</div></div>","PeriodicalId":73987,"journal":{"name":"Journal of the National Cancer Center","volume":"5 4","pages":"Pages 379-391"},"PeriodicalIF":9.4,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144723506","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advancements in antibody-drug conjugates as cancer therapeutics","authors":"Jung Yin Fong ,&nbsp;Zhixin Phuna ,&nbsp;Di Yang Chong ,&nbsp;Christophorus Manuel Heryanto ,&nbsp;Yu Shyan Low ,&nbsp;Khang Chiang Oh ,&nbsp;Yan Huen Lee ,&nbsp;Allan Wee Ren Ng ,&nbsp;Lionel Lian Aun In ,&nbsp;Michelle Yee Mun Teo","doi":"10.1016/j.jncc.2025.01.007","DOIUrl":"10.1016/j.jncc.2025.01.007","url":null,"abstract":"<div><div>Antibody-drug conjugates (ADCs) represent a promising approach in targeted cancer therapy, combining the targeted precision of antibodies with the potency of cytotoxic payloads to selectively target tumour cell whilst minimising off-target effects. This review provides a comprehensive analysis of ADCs, encompassing their structural components, mechanisms of action, and clinical applications. It also examines recent technological advancements, particularly in antibody engineering and linker design, aimed at enhancing therapeutic efficacy and safety. The current clinical landscape is outlined, highlighting approved ADCs and promising candidates in clinical trials, while also addressing key challenges such as stability, half-life, and systemic toxicity. This review is based on an extensive literature survey from major databases such as Scopus and Web of Science, with a focus on keywords like “antibody-drug conjugates”, “ADC advancements”, and “next-generation ADC technologies”. By integrating insights from both preclinical and clinical perspectives, we highlight the transformative potential of ADCs in advancing modern cancer therapy.</div></div>","PeriodicalId":73987,"journal":{"name":"Journal of the National Cancer Center","volume":"5 4","pages":"Pages 362-378"},"PeriodicalIF":9.4,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144723494","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}