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Exploring the potential of extrachromosomal DNA as a novel oncogenic driver

Science China Life Sciences 2025年第1期 144-157页

作者： Huanbo Zhu Longtao Huangfu Junbing Chen Jiafu Ji Xiaofang Xing Key Laboratory of Carcinogenesis and Translational research (Ministry of Education/Beijing) Division of Gastrointestinal Cancer Translational Research LaboratoryPeking University Cancer Hospital & Institute Department of Gastrointestinal cancer Center Peking University Cancer Hospital & Institute Department of Liver Surgery & Transplantation Liver Cancer InstituteZhongshan HospitalFudan University Key Laboratory of Carcinogenesis and cancer Invasion Ministry of Education State Key Laboratory of Holistic Integrative Management of Gastrointestinal cancers Beijing Key Laboratory of Carcinogenesis and Translational ResearchDivision of Gastrointestinal Cancer Translational Research LaboratoryPeking University Cancer Hospital & Institute

Extrachromosomal DNA(ecDNA) is a form of circular DNA mostly found in tumor cells. Unlike the typical chromosomal DNA, ecDNA is circular, self-replicating, and carries complete or partial gene fragments. Although ecDNA occurrence remains a rare event in cancer, recent studies have shown that oncogene amplification on ecDNA is widespread throughout many types of cancer, implying that ecDNA plays a central role in accelerating tumor evolution. ecDNA has also been associated with increased tumor mutation burden, chromosomal instability, and even tumor microenvironment remodeling. ecDNA may be crucial in influencing tumor heterogeneity, drug sensitivity,oncogenic senescence, and tumor immunogenicity, leading to a worsening prognosis for tumor patients. In this way, several clinical trials have been conducted to investigate the importance of ecDNA in clinical treatment. In this review, we summarize the biogenesis, characteristics, and current research methods of ecDNA, discuss the vital role of ecDNA-caused tumor heterogeneity in cancers, and highlight the potential role of ecDNA in cancer therapy.

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Can patients with mild non-neoplastic lesions diagnosed at baseline screening be safely exempt from surveillance: evidence from multicenter community-based cohorts

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Science China Life Sciences 2025年第1期 263-271页

作者： Siyi He Zhiyi Zhang Guohui Song Zhenhai Wang Chunyun Dai Shipeng Yan Kun Jiang Bingbing Song He Li Maomao Cao Dianqin Sun Fan Yang Xinxin Yan Shaoli Zhang Yi Teng Qianru Li Changfa Xia Wanqing Chen Office of cancer Screening National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical College Department of Gastroenterology Gansu Wuwei Tumor Hospital Cixian cancer Institute Linzhou cancer Hospital Center for Disease Control and Prevention of Sheyang County Department of cancer Prevention and Control Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of MedicineCentral South University Luoshan Center for Disease Control and Prevention Office for cancer Control and research Affiliated Cancer Hospital of Harbin Medical University

Surveillance recommendations for gastric cancer（GC） in current guidelines focused on advanced precancerous lesions and were based on precise diagnosis of severity/extent of baseline lesions. We aimed to develop a less endoscopy-related equipment-dependent risk-stratification tool, and assessed whether mild-precursor-lesion patients can be safely exempt from surveillance. In the multicenter communitybased cohort, 75,051 participants receiving baseline endoscopy were enrolled during 2015–2017 and followed-up until 2021. Cumulative incidence rates（CIRs） of GC for precancerous-conditions were calculated by Kaplan-Meier method and compared by Log-rank tests. Mixedeffects Cox regression models were used to detect potential factors for progression towards GC. A risk score was calculated as counts of selected factors. An independent cohort, including 26,586 participants was used for external validation. During a median follow-up of 6.25 years, CIRs of GC were 0.302%, 0.436%, and 4.756% for normal group, non-neoplastic（atrophic gastritis/intestinal metaplasia） and neoplastic lesions（low-grade/high-grade dysplasia）, respectively(Ptrend<0.001). Four predictors, including male, ≥60 years, smoking, and limited vegetable consumption, were selected for risk-stratification. High-risk patients（≥3 risk factors） with non-neoplastic lesions showed higher GC risks（adjusted HR=7.73, 95%CI: 4.29–13.92）, and their four-year CIR reached the one-year CIR of neoplastic lesions. Further categorizing non-neoplastic lesions by histological grade, both patients with moderate-to-severe lesions（aHR=3.07, 95%CI: 1.67–5.64） and high-risk patients with mild lesions（aHR=7.29, 95%CI: 3.58–14.86） showed higher risks. Consistent trends were observed in validation cohort. High-risk mild-precursor-lesion patients should receive surveillance within 3–5 years after baseline screening. Our study provides evidence on supplementing current guideline recommendations.

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Antithetical impacts of deleterious LRP1B mutations in non-squamous and squamous NSCLCs on predicting benefits from immune checkpoint inhibitor alone or with chemotherapy over chemotherapy alone: retrospective analyses of the POPLAR/OAK and CHOICE-01 trial

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Science China Life Sciences 2025年第1期 249-262页

作者： Jinliang Wang Wenyong Zhou Yu Xu Jianchun Duan Qiaoxia Zhou Guoqiang Wang Leo Li Chunwei Xu Wenxian Wang Shangli Cai Zhijie Wang Jie Wang Department of Oncology The Fifth Medical Center of Chinese PLA General Hospital Department of Thoracic Surgery Shanghai Chest HospitalSchool of MedicineShanghai Jiao Tong University Burning Rock Biotech CAMS Key Laboratory of Translational research on Lung cancer State Key Laboratory of Molecular OncologyDepartment of Medical OncologyNational Cancer Center/National Clinical Research Center for ancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical College Institute of Basic Medicine and cancer (IBMC) Chinese Academy of Sciences Department of Clinical Trial The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital)

In non-small cell lung cancers,the non-squamous and squamous subtypes（nsqNSCLC and sqNSCLC） exhibit disparities in pathophysiology,tumor immunology,and potential genomic correlates affecting responses to immune checkpoint inhibitor（ICI）-based *** our inhouse training cohort（n=85）,the presence of the LRP1B deleterious mutation（LRP1B-del） was associated with longer and shorter progression-free survival（PFS） on ICIs alone in nsqNSCLCs and sqNSCLCs,respectively(Pinteraction=0.008).These results were validated using a larger public ICI cohort(n=208,Pinteractioncancer therapeutics.

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Antisense oligonucleotides provide optimism to the therapeutic landscape for tauopathies

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Neural Regeneration research 2025年第3期20卷 803-804页

作者： Glenn A.Harris Lauren R.Hirschfeld Rainwater Charitable foundation Fort WorthTXUSA

Tauopathies are a group of neurodegenerative diseases characterized by abnormal metabolism of the misfolded tau protein. Tau is encoded by the microtubule-associated protein tau gene(MAPT) and can be classified as either 3-repeat(3R) or 4-repeat(4R) based on the number of repeat domains from alternative splicing of exon 10 of the MAPT gene.

关键词： tau metabolism diseases

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AZD1775 synergizes with SLC7A11 inhibition to promote ferroptosis

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Science China Life Sciences 2025年第1期 204-218页

作者： Chen Xiong Hong Ling Yingdan Huang Hanzhi Dong Bangxiang Xie Qian Hao Xiang Zhou Fudan University Shanghai cancer Center and Institutes of Biomedical Sciences Fudan University Department of Oncology Shanghai Medical CollegeFudan University Department of Breast Surgery Fudan University Shanghai Cancer CenterFudan University Department of Oncology First Affiliated Hospital of Nanchang University Beijing Institute of Hepatology Beijing Youan HospitalCapital Medical University Beijing Engineering research Center for Precision Medicine and Transformation of Hepatitis and Liver cancer Key Laboratory of Breast cancer in Shanghai Fudan University Shanghai Cancer CenterFudan University Shanghai Key Laboratory of Medical Epigenetics International Co-laboratory of Medical Epigenetics and Metabolism (Ministry of Science and Technology)Institutes of Biomedical SciencesFudan University

Tumor suppressor p53-mediated cell cycle arrest and DNA damage repair may exert cytoprotective effects against cancer therapies, including WEE1 inhibition. Considering that p53 activation can also lead to multiple types of cell death, the role of this tumor suppressor in WEE1 inhibitor-based therapies remains disputed. In this study, we reported that nucleolar stress-mediated p53 activation enhanced the WEE1 inhibitor AZD1775-induced ferroptosis to suppress lung cancer growth. Our findings showed that AZD1775 promoted ferroptosis by blocking cystine uptake, an action similar to that of Erastin. Meanwhile, inhibition of WEE1 by the WEE1 inhibitors or si RNAs induced compensatory upregulation of SLC7A11, which conferred resistance to ferroptosis. Mechanistically, AZD1775 prevented the enrichment of H3K9me3, a histone marker of transcriptional repression, on the SLC7A11 promoter by repressing the expression of the histone methyltransferase SETDB1, thereby enhancing NRF2-mediated SLC7A11 transcription. This finding was also validated using the H3K9me3 inhibitor BRD4770. Remarkably, we found that the nucleolar stress-inducing agent Actinomycin D(Act. D) inhibited SLC7A11 expression by activating p53, thus augmenting AZD1775-induced ferroptosis. Moreover, the combination of AZD1775 and Act. D synergistically suppressed wild-type p53-harboring lung cancer cell growth both in vitro and in vivo. Altogether, our study demonstrates that AZD1775 promotes ferroptosis by targeting cystine uptake but also mediates the adaptive activation of SLC7A11 through the WEE1-SETDB1 cascade and NRF2-induced transcription, and inhibition of SLC7A11 by Act. D boosts the anti-tumor efficacy of AZD1775 by enhancing ferroptosis in cancers with wild-type p53.

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International Szent-Gyorgyi Prize for Progress in cancer research:basic and translational research recognition Mary-Claire King received the 2016 Prize for her pioneering research that demonstrated the first evidence of genetic predisposition to breast cancer

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Chinese Journal of cancer 2017年第11期36卷 533-536页

作者： Hali Hartmann Jie Zhao Sujuan Ba National foundation for cancer research

The Szent-Gy?rgyi Prize for Progress in cancer research is a prestigious scientific award sponsored by the National foundation for cancer research(NFCR)-a leading cancer research charitable organization in the United States that supports innovative cancer research globally with the ultimate goal to cure cancer. The coveted Szent-Gy?rgyi Prize annually honors a scientist whose seminal discovery or body of work has resulted in, or led toward, notable contributions to cancer prevention, diagnosis, or treatment; and the discovery has had a high direct impact of saving people's lives. In addition, the prize promotes public awareness of the importance of basic cancer research and encourages the sustained investment needed to accelerate the translation of these research discoveries into new cancer treatments. In 2016, NFCR's Szent-Gy?rgyi Prize Selection Committee was unanimous in its decision to recognize an icon in human disease genetics, Dr. Mary-Claire King, for her pioneering research that demonstrated the first evidence of genetic predisposition to breast cancer. Her proof of existence of BRCA1 gene and its location has made genetic screening for breast and ovarian cancers possible, saving lives of many people who are at high risk with inherited BRCA1 mutations.

关键词： The National foundation for cancer research The Szent-Gyorgyi Prize Mary-Claire King BRCA1 and genetic testing

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Record-breaking bifunctional oxygen electrocatalyst accomplished by a data-driven approach for zinc-air batteries

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Journal of Energy Chemistry 2025年第1期100卷 144-145页

作者： Deviprasath Chinnadurai Zhi Wei Seh Institute of Materials research and Engineering (IMRE) Agency for Science Technology and Research (A*STAR)

Rechargeable zinc-air batteries(ZABs) have recently drawn great attention in energy research due to their high theoretical capacity,low costs, and inherently safe nature [1–3]. However, the sluggish cathode reactions necessitate the development of bifunctional oxygen electrocatalysts with lower ΔE indicator values. The ΔE indicator is commonly employed to quantitatively evaluate the electrocatalytic activity of a bifunctional oxygen electrocatalyst,representing the overall overpotential from oxygen reduction reaction(ORR) to oxygen evolution reaction(OER).

关键词： Data-driven approach Bifunctional oxygen electrocatalyst Record breaking performance Zinc-air batteries

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Effective extraction of polyribosomes from astrocytes enables future discoveries on translation regulation

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Neural Regeneration research 2025年第4期20卷 1083-1084页

作者： Orna Elroy-Stein Sagol School of Neuroscience Tel Aviv UniversityTel AvivIsrael Shmunis School of Biomedicine and cancer research George S.Wise Faculty of Life SciencesTel Aviv UniversityTel AvivIsrael

Translation regulation is an important layer of gene expression:Generation of genome-wide expression datasets at multi-omics levels in spatial,temporal,and cell-type resolution is essential for deciphering brain *** of gene expression is a highly dynamic process aiming at the production of precise levels of gene products to guarantee optimal cellular function,in response to physiological *** advances in next-generation sequencing enabled the understanding of epigenomic and transcriptomic dynamic landscapes of different brain regions along development,aging,and disease ***,the correlation of the“transcriptome”with protein levels is poor because numerous mRNAs are subjected to manipulation of their translation efficiency,to warrant a favorable result under certain ***,it is widely accepted that regulation at the translation level is a vital layer of gene *** of actively translated mRNA populations(i.e.,“translatome”)is a more reliable predictor of the“proteome”(Wang et al.,2020).

关键词： translation enable landscape

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Personalized immunotherapy in cancer precision medicine

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cancer Biology & Medicine 2021年第4期18卷 955-965页

作者： Kazuma Kiyotani Yujiro Toyoshima Yusuke Nakamura Project for Immunogenomics Cancer Precision Medicine CenterJapanese Foundation for Cancer ResearchTokyo 135-8550Japan

With the significant advances in cancer genomics using next-generation sequencing technologies,genomic and molecular profilingbased precision medicine is used as a part of routine clinical test for guiding and selecting the most appropriate treatments for individual cancer *** many molecular-targeted therapies for a number of actionable genomic alterations have been developed,the clinical application of such information is still limited to a small proportion of cancer *** this review,we summarize the current status of personalized drug selection based on genomic and molecular profiling and highlight the challenges how we can further utilize the individual genomic *** immunotherapies,including immune checkpoint inhibitors,would be one of the potential approaches to apply the results of genomic sequencing most *** cancer-specific antigens derived from somatic mutations,the so-called neoantigens,occurring in individual cancers have been in focus *** immunotherapies,which target neoantigens,could lead to a precise treatment for cancer patients,despite the challenge in accurately predicting neoantigens that can induce cytotoxic T cells in individual *** prediction of neoantigens should accelerate the development of personalized immunotherapy including cancer vaccines and T-cell receptor-engineered T-cell therapy for a broader range of cancer patients.

关键词： Personalized medicine cancer precision medicine neoantigen personalized immunotherapy immune checkpoint blockade cancer vaccine adoptive T cell therapy

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Preliminary prospective study of real-time post-gastrectomy glycemic fluctuations during dumping symptoms using continuous glucose monitoring

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World Journal of Gastroenterology 2021年第23期27卷 3386-3395页

作者： Motonari Ri Souya Nunobe Satoshi Ida Naoki Ishizuka Shinichiro Atsumi Rie Makuuchi Koshi Kumagai Manabu Ohashi Takeshi Sano Department of Gastroenterological Surgery Cancer Institute HospitalJapanese Foundation for Cancer ResearchTokyo 135-8550Japan Clinical Trial Planning and Management Cancer Institute HospitalJapanese Foundation for Cancer ResearchTokyo 135-8550Japan

BACKGROUND Although dumping symptoms constitute the most common post-gastrectomy syndromes impairing patient quality of life,the causes,including blood sugar fluctuations,are difficult to elucidate due to limitations in examining dumping symptoms as they *** To investigate relationships between glucose fluctuations and the occurrence of dumping symptoms in patients undergoing gastrectomy for gastric *** Patients receiving distal gastrectomy with Billroth-I(DG-BI)or Roux-en-Y reconstruction(DG-RY)and total gastrectomy with RY(TG-RY)for gastric cancer(March 2018-January 2020)were prospectively *** tissue glycemic profiles were measured every 15 min,up to 14 d,by continuous glucose *** episodes were recorded on 5 patient-selected days by *** 3 h postprandially,dumping-associated glycemic changes were defined as a dumping profile,those without symptoms as a control *** profiles were *** Thirty patients were enrolled(10 DG-BI,10 DG-RY,10 TG-RY).The 47 early dumping profiles of DG-BI showed immediately sharp rises after a meal,which 47 control profiles did not(P<0.05).Curves of the 15 late dumping profiles of DG-BI were similar to those of early dumping profiles,with lower glycemic *** and TG-RY late dumping profiles(7 and 13,respectively)showed rapid glycemic decreases from a high glycemic state postprandially to hypoglycemia,with a steeper drop in TG-RY than in *** Postprandial glycemic changes suggest dumping symptoms after standard gastrectomy for gastric ***,glycemic profiles during dumping may differ depending on reconstruction methods after gastrectomy.

关键词： Gastric cancer Gastrectomy Billroth-I reconstruction Roux-en-Y reconstruction Dumping syndrome Continuous glucose monitoring

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