Cancer Communications最新文献

{"title":"Advances in radiopharmaceuticals for cancer radiotheranostics: CCK2R targeting as a paradigm for translational innovation.","authors":"Jing Li, Xuejun Wen, Rebeka Rita Reszegi, Hemavarshini Kamalrhaj, Wolfgang J Parak, Xiaoyuan Chen, Jingjing Zhang","doi":"10.1002/cac2.70063","DOIUrl":"https://doi.org/10.1002/cac2.70063","url":null,"abstract":"<p><p>Radiopharmaceuticals are reshaping the landscape of cancer therapy, offering a unique theranostic advantage that is becoming increasingly central to precision medicine. By labeling the same molecular scaffold with different radionuclides, these agents enable seamless integration of diagnostic imaging and targeted therapy. Clinical breakthroughs with somatostatin receptor subtype 2 (SSTR2)- and prostate-specific membrane antigen (PSMA)-targeted radiopharmaceuticals have significantly enhanced both tumor visualization and therapeutic efficacy, establishing new benchmarks in oncology. Ongoing research is exploring novel molecular targets such as cholecystokinin-2 receptor (CCK2R), fibroblast activation protein (FAP), and C-X-C chemokine receptor type 4 (CXCR4). In parallel, there is growing interest in utilizing alternative radionuclides, including alpha-particle emitters and Auger electron emitters, beyond the commonly used beta-emitters, to improve therapeutic outcomes. Simultaneously, advances in ligand and linker design are being leveraged to optimize in vivo pharmacokinetics and tissue distribution. Among the emerging targets, CCK2R has attracted notable attention due to its overexpression in multiple malignancies. Research efforts have focused on improving ligand stability, receptor-binding affinity, and tumor retention, while also exploring strategies to enhance CCK2R expression on cancer cells. This review offers a comprehensive overview of the current landscape in cancer radiotheranostics, exploring the role of CCK2R in cancer biology and summarizing the latest advancements in the development of CCK2R-targeted radiopharmaceuticals. Using these advancements as a case study, we systematically examine key aspects of next-generation radiopharmaceutical design, from target selection and ligand engineering to pharmacokinetic optimization and clinical translation, providing a multidimensional framework for future innovation in cancer radiotheranostics.</p>","PeriodicalId":9495,"journal":{"name":"Cancer Communications","volume":" ","pages":""},"PeriodicalIF":24.9,"publicationDate":"2025-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145091262","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to “Improving antitumor immunity using antiangiogenic agents: Mechanistic insights, current progress, and clinical challenges”","authors":"","doi":"10.1002/cac2.70060","DOIUrl":"10.1002/cac2.70060","url":null,"abstract":"<p>Shu-Jin Li¹, Jia-Xian Chen¹, Zhijun Sun^1,2</p><p>¹The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) &amp; Key Laboratory of Oral Biomedicine, Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan 430079, Hubei, People's Republic of China</p><p>²Department of Oral Maxillofacial-Head Neck Oncology, School and Hospital of Stomatology, Wuhan University, Wuhan 430079, Hubei, People's Republic of China</p><p>Shu-Jin Li and Jia-Xian Chen contributed equally to this work.</p><p><b>Correspondence</b>: Zhijun Sun (<span>[email protected]</span>)</p><p>Following the publication of this article [1], it has come to our attention that proper citations were inadvertently omitted when introducing the concept of “immunostimulatory vascular-modulating cycle” and its illustration in Figure 4. The concept was originally proposed by Khan and Kerbel (2018) [2].</p><p>The revised text now reads:</p><p>“<i>An immunostimulatory vascular-modulating cycle has been proposed to explain the synergistic effects observed between antiangiogenic agents and cancer immunotherapy, based on the mutual regulation between vascular normalization and immune responses</i> [2] (Figure 4).”</p><p>The revised Figure 4 is provided below:</p><p>We sincerely apologize for our mistake.</p><p>[1] Li SJ, Chen JX, Sun ZJ. Improving antitumor immunity using antiangiogenic agents: Mechanistic insights, current progress, and clinical challenges. Cancer Commun. 2021;41(9):830–50.</p><p>[2] Khan KA, Kerbel RS. Improving immunotherapy outcomes with anti-angiogenic treatments and vice versa. Nat Rev Clin Oncol. 2018;15(5):310–24.</p>","PeriodicalId":9495,"journal":{"name":"Cancer Communications","volume":"45 10","pages":"1339-1340"},"PeriodicalIF":24.9,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cac2.70060","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145032833","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neoadjuvant chemoradiotherapy with capecitabine and irinotecan guided by UGT1A1 status in patients with locally advanced rectal cancer: 5-year update of the CinClare trial.","authors":"Zhen Zhang, Xinchen Sun, Anwen Liu, Yaqun Zhu, Tao Zhang, Luying Liu, Jianhui Jia, Shisheng Tan, Junxin Wu, Xin Wang, Juying Zhou, Jialin Yang, Chen Zhang, Hongyan Zhang, Xinjia He, Gang Cai, Chengyi Huang, Fan Xia, Juefeng Wan, Hui Zhang, Lijun Shen, Ling Wang, Wei Zhang, Sanjun Cai, Ji Zhu","doi":"10.1002/cac2.70058","DOIUrl":"10.1002/cac2.70058","url":null,"abstract":"<p><strong>Background: </strong>The optimal regimen and chemotherapy intensity are still under investigation for neoadjuvant treatment of locally advanced rectal cancer (LARC). The CinClare trial has demonstrated improved pathologic complete response (pCR) with the addition of irinotecan to neoadjuvant chemoradiotherapy (CRT) guided by uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) genotype in LARC. Here, we report the 5-year follow-up outcomes of the CinClare study.</p><p><strong>Methods: </strong>From November 2015 to December 2017, this randomized, open-label, multicenter, phase III trial enrolled 360 patients with LARC and assigned them in a 1:1 ratio to CapIriRT (radiation with capecitabine combined with irinotecan followed by irinotecan and capecitabine) or CapRT (radiation with concurrent capecitabine followed by oxaliplatin and capecitabine). Irinotecan dosing was guided by UGT1A1 genotype (80 mg/m² for *1/*1 and 65 mg/m² for *1/*28). The endpoints, including local control (LC), distant metastasis-free survival (DMFS), disease-free survival (DFS), and overall survival (OS), were analyzed using the log-rank test, Cox proportional hazards regression and restricted mean survival time (RMST) test at the data cut-off date of June 2023.</p><p><strong>Results: </strong>With a median follow-up of 60 months, the CapIriRT group showed numerically higher 5-year LC (95.6% vs. 93.9%), 5-year DMFS (83.9% vs. 77.9%), 5-year DFS (77.7% vs. 70.6%), and 5-year OS rates (82.9% vs. 76.1%) than the CapRT group. Further RMST test also showed a statistically significant difference in DFS (P < 0.05) and a borderline difference in OS (P = 0.050). Among the UGT1A1 *1/*1 population, the CapIriRT group had significantly improved 5-year rates of DMFS, DFS, and OS (all P < 0.05). Patients achieving pCR also had significantly longer DFS and OS compared to non-pCR patients (P < 0.05).</p><p><strong>Conclusions: </strong>The addition of irinotecan guided by UGT1A1 genotype to a standard capecitabine-based scheme brings clinical benefits with improved LC, DMFS, DFS, and OS. Patients with the UGT1A1 *1/*1 genotype derived notable benefit from irinotecan, with improved survival outcomes. Achievement of pCR is crucial as it is associated with improved long-term survival. These findings support the integration of genomic testing into clinical practice to achieve a personalized irinotecan dosing regimen, which can optimize efficacy and safety.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov (NCT02605265).</p>","PeriodicalId":9495,"journal":{"name":"Cancer Communications","volume":" ","pages":""},"PeriodicalIF":24.9,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144944089","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"EXPRESSION OF CONCERN: Discovery of a Novel Viroid-Like Circular RNA in Colorectal Cancer","authors":"","doi":"10.1002/cac2.70057","DOIUrl":"10.1002/cac2.70057","url":null,"abstract":"<p>Wu M, Li W, Hu N, Liu C, Li J, Li Y, et al. Discovery of a Novel Viroid-Like Circular RNA in Colorectal Cancer. <i>Cancer Commun</i>. 2025;45(1):46-50. doi: 10.1002/cac2.12626.</p><p>This Expression of Concern is for the above article, published online on 09 November 2024 in Wiley Online Library (wileyonlinelibrary.com), and has been issued by agreement between the journal Editor-in-Chief, Rui-Hua Xu; Sun Yat-sen University Cancer Center; and John Wiley &amp; Sons Australia. The Expression of Concern has been agreed upon following information provided by a third party regarding the identification of the CRC-associated viroid. The authors reported this viroid-like circRNA as absent from the human genome based on the hg38 reference. However, the sequence is present at chromosome13:96543662-96543775 in the more complete T2T human genome reference, indicating it is not an exogenous RNA element. The authors have acknowledged the need for further investigation, particularly in light of the discrepancies from the difference between the hg38 and T2T human genomes. The editors have decided to issue this Expression of Concern to alert readers as further investigations proceed.</p>","PeriodicalId":9495,"journal":{"name":"Cancer Communications","volume":"45 10","pages":""},"PeriodicalIF":24.9,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cac2.70057","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144944108","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Risk of colorectal cancer by family history of both colorectal carcinomas and colorectal polyps: a nationwide cohort study.","authors":"Yuqing Hu, Elham Kharazmi, Qunfeng Liang, Hermann Brenner, Jan Sundquist, Kristina Sundquist, Mahdi Fallah","doi":"10.1002/cac2.70059","DOIUrl":"https://doi.org/10.1002/cac2.70059","url":null,"abstract":"<p><strong>Background: </strong>The increased risk of colorectal cancer (CRC) associated with family history of both colorectal in situ or invasive carcinomas (Stage 0 to IV) and colorectal polyps is attributed solely to family history of CRC, resulting in an underestimation of the actual risk. We aimed to assess the association between overall and early-onset CRC (EOCRC) risk and family history of both colorectal carcinomas and polyps.</p><p><strong>Methods: </strong>We conducted a nationwide cohort study leveraging Swedish family-cancer datasets with follow-up from 1964 to 2018. Standardized incidence ratios (SIRs) were calculated to estimate the risk of CRC and EOCRC among individuals with a family history of both colorectal polyps and carcinomas.</p><p><strong>Results: </strong>We followed up 13,432,205 individuals for up to 54 years. The risk of overall CRC was 2.2 times increased in individuals with 1 first-degree relative (FDR) with one-time polyp diagnosis and an additional FDR with carcinoma (95% CI = 2.1-2.3; EOCRC SIR = 2.9 [95% CI = 2.4-3.4]). The risk was significantly higher in individuals with 1 FDR with repeated polyp diagnoses (≥2 times) and an additional FDR with carcinoma (overall SIR = 2.9 [95% CI = 2.7-3.1]; EOCRC SIR = 5.4 [95% CI = 3.9-6.4]). A similar risk was observed in individuals with ≥2 FDRs with one-time polyp diagnosis and an additional FDR with carcinoma (overall SIR = 2.9 [95% CI = 2.4-3.4]; EOCRC SIR = 5.3 [95% CI = 3.0-8.6]). Individuals with ≥2 FDRs with repeated polyp diagnoses and an additional FDR with carcinoma had a 5.0-fold overall risk (95% CI = 4.3-5.7) and a 13.8-fold EOCRC risk (95% CI = 9.7-20.1). Younger age at polyp/carcinoma diagnoses, and more relatives with polyps and carcinomas were associated with higher CRC risk.</p><p><strong>Conclusions: </strong>Individuals with a family history of both colorectal polyps and carcinomas are at significantly increased risk of CRC, especially EOCRC. The risk increased with frequent polyp diagnoses, younger age at first polyp/carcinoma diagnoses, and the number of relatives with polyps/carcinomas. This study highlights the importance of considering both colorectal polyps and carcinomas in family history when assessing CRC risk. These findings could supplement current screening guidelines.</p>","PeriodicalId":9495,"journal":{"name":"Cancer Communications","volume":" ","pages":""},"PeriodicalIF":24.9,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144944154","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lactylation in cancer biology: Unlocking new avenues for research and therapy.","authors":"Xiaoyu Hou, Zhenya Hong, Huimin Zen, Changyi Zhang, Peng Zhang, Ding Ma, Zhiqiang Han","doi":"10.1002/cac2.70054","DOIUrl":"10.1002/cac2.70054","url":null,"abstract":"<p><p>Lactylation, a newly identified post-translational modification, plays a multifaceted role in cancer biology by integrating epigenetic and non-epigenetic mechanisms. This review summarizes the latest research progress on lactylation, including its functions in epigenetic regulation and its broader impact on cellular processes. Lactate, as a metabolic byproduct, not only serves as an energy source for tumor cells but also acts as a signaling molecule driving various oncogenic processes. Lactylation facilitates cancer metabolic reprogramming, enabling tumor cells to adapt to hypoxic and nutrient-deprived microenvironments. Moreover, lactylation mediates immune suppression in the tumor microenvironment, promoting immune evasion and therapy resistance. This review further explores the clinical potential of targeting lactylation, offering new avenues for innovation in cancer research and treatment. These findings highlight the pivotal role of lactylation in cancer progression and its significant value as a potential therapeutic target.</p>","PeriodicalId":9495,"journal":{"name":"Cancer Communications","volume":" ","pages":""},"PeriodicalIF":24.9,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144882264","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Harnessing chimeric antigen receptor macrophages against solid tumors.","authors":"Mengru Wang, Zhen Qin, Xiu-Wu Bian, Yu Shi","doi":"10.1002/cac2.70053","DOIUrl":"https://doi.org/10.1002/cac2.70053","url":null,"abstract":"<p><p>Macrophages are prevalent in multiple tumors and exhibit diverse and potent functional activities. Therapeutic reprogramming of macrophage phenotypes represents a promising strategy for cancer immunotherapy. Engineering chimeric antigen receptors (CARs) to endow macrophages with anti-tumor capacities demonstrated encouraging efficacy, particularly in enhancing tumor-targeted phagocytosis. Furthermore, CAR macrophages (CAR-Ms) orchestrate adaptive immunity through secreting pro-inflammatory cytokines and presenting tumor antigens, thereby activating cytotoxic T lymphocyte responses. These multifaceted properties establish CAR-Ms as potent immunotherapeutic agents against therapy-refractory solid malignancies. Herein, we delineate the design principles, recent research advances, and rational combination strategies of CAR-Ms, with particular emphasis on emerging clinical evidence from ongoing CAR-M trials. We also explore potential applications of CAR-Ms in non-tumorous diseases and forecast future trends based on CAR-T therapy evolution. CAR-M development, combined with emerging technologies, will generate new perspectives for advancing cancer immunotherapy.</p>","PeriodicalId":9495,"journal":{"name":"Cancer Communications","volume":" ","pages":""},"PeriodicalIF":24.9,"publicationDate":"2025-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144871629","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuroinflammation drives apathy in cancer cachexia","authors":"Bingjun Ha,&nbsp;Xuetao Cao","doi":"10.1002/cac2.70055","DOIUrl":"10.1002/cac2.70055","url":null,"abstract":"&lt;p&gt;Neuro-immune modulation has attracted growing attention in recent years, particularly in elucidating neuro-immune interactions within the tumor microenvironment (TME). The nervous system actively monitors immune activity within the TME, transmits these signals to the brain for integrative processing, and acts back on the TME, forming a neuroimmune regulatory circuit to affect antitumor response and therapeutic outcomes [&lt;span&gt;1&lt;/span&gt;]. Accumulating evidence demonstrates that the nervous system critically regulates tumor metastasis through the release of neurotransmitters and neurotrophic factors [&lt;span&gt;2&lt;/span&gt;]. However, the precise mechanisms by which the nervous system contributes to the pathogenesis of cancer cachexia remain poorly understood. Cancer cachexia represents a multifactorial wasting syndrome characterized by progressive weight loss, muscle atrophy, and metabolic dysregulation, predominantly occurring in advanced-stage cancer patients [&lt;span&gt;3&lt;/span&gt;]. Pro-inflammatory cytokines, particularly Interleukin 6 (IL-6) and tumor necrosis factor-α (TNF-α; historically termed cachectin), have been extensively implicated in tumor progression [&lt;span&gt;4&lt;/span&gt;]. These mediators promote cachexia through direct actions on muscle and adipose tissue [&lt;span&gt;3&lt;/span&gt;]. Beyond their established roles in metabolic dysregulation and muscle wasting, these cytokines are increasingly recognized for their involvement in cytokine release syndrome associated with new-generation cancer immunotherapies, including immune checkpoint inhibitors and chimeric antigen receptor T (CAR-T) cell therapy [&lt;span&gt;5&lt;/span&gt;]. Notably, IL-6 exhibits pleiotropic functions in neural regulation. Social stress exposure induces structural and functional alterations in the blood-brain barrier (BBB), enabling increased extravasation of circulating IL-6 into brain regions implicated in affective regulation, ultimately driving the manifestation of depressive symptoms [&lt;span&gt;6&lt;/span&gt;]. Given its dual role in neuroinflammation and metabolic dysregulation, IL-6 may contribute to the pathogenesis of cachexia-associated neurological symptoms. Despite these advances, the neurobehavioral manifestations of cachexia, particularly depression-like behaviors, remain virtually unexplored. While systemic inflammation is known to impair diverse neurological functions, how cachexia induces these behaviors through central nervous system (CNS) mechanisms remains to be determined.&lt;/p&gt;&lt;p&gt;In a recent study, Zhu et al. [&lt;span&gt;7&lt;/span&gt;] addressed this critical knowledge gap by demonstrating how IL-6 modulates cachexia-associated apathy. To investigate the impact of cachexia on motivation, they used a preclinical model of subcutaneous colon cancer-bearing mice. To account for individual differences in disease progression, they aligned the variable cachexia onset data to the endpoint and found that the most significant weight loss occurred during the last 3 days before death. In the motivation behavior as","PeriodicalId":9495,"journal":{"name":"Cancer Communications","volume":"45 10","pages":"1334-1337"},"PeriodicalIF":24.9,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cac2.70055","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144834056","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Coordinated gene expression within sustained STAT3-associated chromatin conformations contributes to hepatocellular carcinoma progression","authors":"Sunyoung Jang,&nbsp;Sumin Yoon,&nbsp;Hyeokjun Yang,&nbsp;Nayun Choi,&nbsp;Su-Hyang Han,&nbsp;Lark Kyun Kim,&nbsp;Hyoung-Pyo Kim,&nbsp;Jong Hoon Park,&nbsp;Daeyoup Lee,&nbsp;Kyung Hyun Yoo","doi":"10.1002/cac2.70049","DOIUrl":"10.1002/cac2.70049","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Background&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Phosphorylated signal transducer and activator of transcription 3 (p-STAT3) has emerged as a critical modulator of hepatocellular carcinoma (HCC) progression. However, its role in three-dimensional (3D) chromatin conformation and the expression of genes linked to HCC aggressiveness remains largely unexplored. This study aimed to identify HCC 3D chromatin conformations that are regulated by sustained STAT3 activation and validate the molecular mechanisms underlying the aggressiveness of HCC.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Comparative analyses were performed using HCC cell lines with varying levels of STAT3 activation. Chromatin immunoprecipitation-sequencing (ChIP-seq) for p-STAT3 and H3K27ac was conducted to map p-STAT3-associated genomic regions and assess its influence on chromatin states. Chromatin conformation sequencings (high-throughput chromosome conformation capture and high-throughput chromosome conformation capture followed by immunoprecipitation) were employed to investigate the 3D genome landscape and identify conformational changes linked to sustained p-STAT3 activation. RNA-sequencing was performed to assess transcriptional changes in response to these chromatin rearrangements. Functional assays, including invasion and tube formation assays, were carried out to validate the phenotypic impact of p-STAT3 activation on HCC progressiveness. Pharmacological inhibition of STAT3 was tested to explore potential therapeutic avenues and resistance mechanisms.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;We found that sustained activation of p-STAT3 was significantly associated with poor prognostic outcomes in HCC patients. ChIP-seq demonstrated that p-STAT3 regulated chromatin interactions, leading to the formation of frequently interacting regions (FIREs), stable structural units within the 3D genome. Genes within these p-STAT3-associated FIREs exhibited coordinated expression, with many involved in aggressiveness HCC phenotypes like invasion and tube formation. Chromatin conformation data indicated that these FIREs altered topologically associating domains (TADs), potentially influencing broader chromatin organization. Despite STAT3 inhibition, p-STAT3-associated chromatin conformations remained intact, maintaining the expression of genes within FIREs and contributing to drug resistance.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Conclusions&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Sustained p-STAT3 activation significantly alters the 3D chromatin conformation in HCC, particularly through the formation of FIREs. These p-STAT3-associ","PeriodicalId":9495,"journal":{"name":"Cancer Communications","volume":"45 10","pages":"1309-1333"},"PeriodicalIF":24.9,"publicationDate":"2025-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cac2.70049","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144717613","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Short-chain acyl post-translational modifications in cancers: Mechanisms, roles, and therapeutic implications","authors":"Ting Wu,&nbsp;Yingqi Zhao,&nbsp;Xin Zhang,&nbsp;Yuanhe Wang,&nbsp;Qiuchen Chen,&nbsp;Mingrong Zhang,&nbsp;Huan Sheng,&nbsp;Yuying Zhang,&nbsp;Jinyu Guo,&nbsp;Jun Li,&nbsp;Yuxuan Fan,&nbsp;Ziqing Wang,&nbsp;Yalun Li,&nbsp;Haoran Wang,&nbsp;Minjie Wei,&nbsp;Xiaoyun Hu,&nbsp;Huizhe Wu","doi":"10.1002/cac2.70048","DOIUrl":"10.1002/cac2.70048","url":null,"abstract":"<p>Post-translational modifications (PTMs) play a pivotal role in epigenetic regulation and are key pathways for modulating protein functionality. PTMs involve the covalent attachment of distinct chemical groups, such as succinyl, crotonyl, and lactyl, at specific protein sites, which alter protein structure, function, stability, and activity, ultimately influencing biological processes. Recently, metabolically derived short-chain acylation modifications (with acyl groups containing fewer than six carbon atoms) have been progressively identified, such as butyrylation, succinylation, crotonylation, and lactylation, differing from traditional acetylation in structure, physicochemical properties, function, and regulation. Aberrant short-chain acyl-PTMs are often associated with tumorigenesis. Research highlights that PTMs like succinylation and lactylation are essential in regulating tumor metabolism, drug resistance, and immune responses. This review elucidates the regulatory mechanisms of eight short-chain acyl-PTMs—butyrylation, succinylation, crotonylation, malonylation, glutarylation, 2-hydroxyisobutyrylation, β-hydroxybutyrylation, and lactylation—that are involved in tumor initiation and progression. Their roles in controlling tumor genomic stability, gene transcription, protein stability, enzyme activity, and nuclear localization are summarized, demonstrating their impact on related biological processes such as tumor metabolism, multi-drug resistance, and immune evasion. Additionally, the review provides an overview of current drug research targeting enzymes that regulate PTMs, offering critical insights to advance therapeutic strategies for cancer treatment.</p>","PeriodicalId":9495,"journal":{"name":"Cancer Communications","volume":"45 10","pages":"1247-1284"},"PeriodicalIF":24.9,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cac2.70048","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144697695","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}