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Chinese Journal of Natural medicines 2024年第9期22卷 864-868页

作者： HE Shiting ZOU Qinghui ZHANG Qi LUO Yingming YAN Die HE Jingxin LIU Yena CUI Hui School of Pharmaceutical Sciences Guangzhou University of Chinese MedicineGuangzhou 510006China state key laboratory of oncology in south china Collaborative Innovation Center for Cancer MedicineSun Yat-Sen University Cancer CenterGuangzhou 510060China

Three novel sesterterpenoids glasesterterpenoids A-C(1-3),featuring an unprecedented 7-cyclohexyldecahydronaphthalene carbon skeleton,were isolated from the root of Lindera glauca(***).Their structures were elucidated by quantum chemical calculations and spectroscopic *** biogenetic pathway for 1-3 is *** the bioassay,glasesterterpenoid C exhibited DNA topoisomerase 1(Top1)inhibitory activity compared with the positive control,*** findings represent the first examples of sesterterpenoids with a 7-cyclohexyldecahydronaphthalene carbon skeleton from the root of ***.

关键词： Sesterterpenoids Lindera glauca

Mutations in Ras homolog family member A in patients with peripheral T-cell lymphoma and implications for personalized medicine

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cancer Biology & medicine 2024年第9期21卷 754-768页

作者： Lina Hu Xuanye Zhang Shengbing Zang Sun Yat-sen University cancer center State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer Medicine Department of Pathology Sun Yat-sen University Cancer Center Department of Medical oncology Sun Yat-sen University Cancer Center

Genome sequencing has revealed frequent mutations in Ras homolog family member A(RHOA) among various cancers with unique aberrant profiles and pathogenic effects, especially in peripheral T-cell lymphoma(PTCL). The discrete positional distribution and types of RHOA amino acid substitutions vary according to the tumor type, thereby leading to different functional and biological properties, which provide new insight into the molecular pathogenesis and potential targeted therapies for various tumors. However, the similarities and discrepancies in characteristics of RHOA mutations among various histologic subtypes of PTCL have not been fully elucidated. Herein we highlight the inconsistencies and complexities of the type and location of RHOA mutations and demonstrate the contribution of RHOA variants to the pathogenesis of PTCL by combining epigenetic abnormalities and activating multiple downstream pathways. The promising potential of targeting RHOA as a therapeutic modality is also outlined. This review provides new insight in the field of personalized medicine to improve the clinical outcomes for patients.

关键词： Drug target Ras homolog family member A mutation pathogenesis peripheral T-cell lymphoma personalized medicine

QL1706 (anti-PD-1 IgG4/CTLA-4 antibody) plus chemotherapy with or without bevacizumab in advanced non-small cell lung cancer: a multi-cohort, phase II study

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Signal Transduction and Targeted Therapy 2024年第2期9卷 797-806页

作者： Yan Huang Yunpeng Yang Yuanyuan Zhao Hongyun Zhao Ningning Zhou Yaxiong Zhang Likun Chen Ting Zhou Gang Chen Ting Wu Lu Lu Shilin Xue Xiaoyan Kang Li Zhang Wenfeng Fang Department of Medical oncology Sun Yat-sen University Cancer CenterState Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer MedicineNo.651 Dongfeng East RoadGuangzhouGuangdong 510060China Department of medicine Qilu Pharmaceutical Co.Ltd.JinanChina

First-line chemoimmunotherapy(with or without bevacizumab)has improved outcomes in advanced non-small cell lung cancer(NSCLC).Here,this open-label,multi-cohort phase II study(NCT05329025)was done to investigate the safety and efficacy of QL1706(a single bifunctional MabPair product against PD-1 and CTLA-4)and chemotherapy with or without bevacizumab in this *** were enrolled into five different cohorts based on genotype(cohorts 1-4,epidermal growth factor receptor[EGFR]wild-type;cohort 5,EGFR-mutant and progressed on EGFR-tyrosine kinase inhibitors[TKIs]).Between June 11,2021 and December 29,2021,91 patients were *** frequent treatment-related adverse events(TRAEs)included decreased appetite(60[65.9%]),anemia(60[65.9%]),infusion-related reactions(48[52.7%]),and pruritus(44[48.4%]).Grade≥3 TRAEs occurred in 30(33.0%)***-seven(45%)patients with wild-type EGFR achieved partial response(PR)(objective response rate[ORR]=45%)and had a median progression-free survival(mPFS)of 6.8 months(95%CI:5.2-9.7).For 31 patients harboring mutated EGFR,17(54.8%)achieved PR(ORR=54.8%),with an mPFS of 8.5 months(95%CI:5.72-not evaluable).Overall,QL1706 plus chemotherapy,regardless of having bevacizumab,was generally tolerable and had promising antitumor activity for EGFR wild-type advanced NSCLC in first-line ***,QL1706 plus chemotherapy and bevacizumab showed favorable antitumor activity for patients who had EGFR mutated NSCLC but failed in TKI therapy,demonstrating a potential for treating this population.

关键词： bevacizumab chemotherapy phase

N6-methyladenosine facilitates mitochondrial fusion of colorectal cancer cells via induction of GSH synthesis and stabilization of OPA1 mRNA

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National Science Review 2024年第3期11卷 72-91页

作者： Jiawang Zhou Haisheng Zhang Ke Zhong Lijun Tao Yu Lin Guoyou Xie Yonghuang Tan You Wu Yunqing Lu Zhuojia Chen Jiexin Li Xin Deng Qin Peng Zigang Li Hongsheng Wang Guangdong Provincial key laboratory of New Drug Design and Evaluation School of Pharmaceutical Sciences Sun Yat-sen University Sun Yat-sen University cancer center State Key Laboratory of Oncology in South China and Collaborative Innovation Center for Cancer Medicine Department of Biomedical Sciences City University of Hong Kong Institute of Systems and Physical Biology Shenzhen Bay Laboratory

Mitochondria undergo fission and fusion that are critical for cell survival and cancer development, while the regulatory factors for mitochondrial dynamics remain elusive. Herein we found that RNA m6A accelerated mitochondria fusion of colorectal cancer（CRC） cells. Metabolomics analysis and function studies indicated that m6A triggered the generation of glutathione（GSH） via the upregulation of RRM2B——a p53-inducible ribonucleotide reductase subunit with anti-reactive oxygen species potential. This in turn resulted in the mitochondria fusion of CRC cells. Mechanistically, m6A methylation of A1240 at 3 UTR of RRM2B increased its m RNA stability via binding with IGF2BP2. Similarly, m6A methylation of A2212 at the coding sequence（CDS） of OPA1——an essential GTPase protein for mitochondrial inner membrane fusion——also increased m RNA stability and triggered mitochondria fusion. Targeting m6A through the methyltransferase inhibitor STM2457 or the dm6ACRISPR system significantly suppressed mitochondria fusion. In vivo and clinical data confirmed the positive roles of the m6A/mitochondrial dynamics in tumor growth and CRC progression. Collectively, m6A promoted mitochondria fusion via induction of GSH synthesis and OPA1 expression, which facilitated cancer cell growth and CRC development.

关键词： m6A mitochondrial fusion glutathione OPA1 colorectal cancer

RNA ac^(4)C modification in cancer biology:from regulatory mechanisms to clinical applications

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Science china(Life Sciences) 2024年第4期67卷 832-835页

作者： Lijun Tao Yunqing Lu Zhuojia Chen Lichen Ge Junming He Jianxin Peng Hongsheng Wang School of Pharmaceutical Sciences Sun Yat-sen UniversityGuangzhou 510006China Sun Yat-sen University cancer center State Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer MedicineGuangzhou 510060China Department of Hepatobiliary Surgery Guangdong Province Traditional Chinese Medical HospitalGuangzhou 510120China

RNA modifications are increasingly recognized for their significance in diverse physiological and pathological processes,with over 170 types of chemical modifications having been discovered since *** these modifications,N4-acetylcytidine(ac^(4)C)is the first acetylated modification identified on eukaryotic RNAs,previously reported in transfer RNA(t RNA)and ribosomal RNA(rRNA)。

关键词： clinical (4) modification

The genomic and immunogenomic landscape of mechanics pathway informs clinical prognosis and response to mechanotherapy

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Science china(Life Sciences) 2024年第8期67卷 1549-1562页

作者： Peidong Zhang Peiwei Li Muya Tang Ryan CGimple Liang Huang Jing Yue Qiuhong Shen Yiwei Du Qian Zhang Zhengnan Yang Haihuai He Kailin Yang Linjie Zhao Shengtao Zhou Department of Obstetrics and Gynecology Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOEState Key Laboratory of BiotherapyWest China Second HospitalSichuan University and Collaborative Innovation CenterChengdu 610041China Physician Scientist Training Program Department of MedicineWashington University School of MedicineSt.Louis 63110USA Department of Neurosurgery State Key Laboratory of BiotherapyWest China HospitalSichuan University and Collaborative Innovation CenterChengdu 610041China Department of Radiation oncology Taussig Cancer CenterCleveland ClinicCleveland 44106USA

Mechanics shape cell and tissue plasticity and maintain their *** cancers,mechanical signals regulate cancer hallmarks via mechanotransduction pathways,such as proliferation,metastasis and metabolic ***,comprehensive characterization of mechanotransduction pathway genes and their clinical relevance across different cancer types remains ***,we systematically portrayed the alterations of mechanotransduction pathway genes across 31 cancer types using The cancer Genome Atlas(TCGA)*** the cancer types could be categorized into 6 subtypes based upon the transcriptional pattern of mechanics pathway *** subtype has its own unique molecular expression pattern,mutation landscapes,immune infiltrates,and patient clinical *** further found that the responses of two subtypes of cancers,one with the optimal outcome and the other with the worst prognosis,to a classical mechanotherapeutic agent(Fasudil,RhoA/ROCK inhibitor)were totally different,indicating that our cancer stratification system based upon mechanotransduction pathway genes could inform clinical responses of patients to mechanotherapeutic ***,our study provides a novel pan-cancer landscape of the mechanotransduction pathways and underscores its potential clinical significance in the prediction of clinical prognosis and therapeutic responses to mechanotherapy among cancer patients.

关键词： pan-cancer cancer mechanics multi-omics immunology

A new autophagy-related nomogram and mechanism in multiple myeloma

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Genes & Diseases 2024年第5期11卷 29-32页

作者： Hanying Huang Yang Li Ziang Zhu Yang Liu Weida Wang Shuzhao Chen Xiaoping Wu Yun Wang Yanzhou Chen Huanxin Lin Yang Liang Lingling Shu state key laboratory of oncology in south china Collaborative Innovation Center for Cancer MedicineSun Yat-sen University Cancer CenterGuangzhouGuangdong 510060China Department of Hematologic oncology Sun Yat-sen University Cancer CenterGuangzhouGuangdong 510060China Department of Radiation oncology Sun Yat-sen University Cancer CenterGuangzhouGuangdong 510060China key laboratory of Neurosurgery in Guangdong Province Southern Medical UniversityGuangzhouGuangdong 510060China Department of Neurosurgery Zhujiang HospitalSouthern Medical UniversityGuangzhouGuangdong 510060China state key laboratory of Pharmaceutical Biotechnology The University of Hong KongHong Kong 999077China

Multiple myeloma(MM)is the second most common hematological *** is characterized by high drug resistance,easy recurrence,and poor prognosis,and remains *** models or scoring modalities can be used to predict the survival prognosis of MM patients;however,these predictions are still not accurate *** have previously found that scorings related to bone marrow microenvironment metabolism can improve predictive efficacy.

关键词： metabolism prognosis myeloma

Microbiota in colorectal cancer related to liver metastasis

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Chinese Journal of cancer Research 2024年第1期36卷 17-24页

作者： Peijun Wei Weiming Han Zitong Zhang Xue Tian Chen Yang Qiaoxuan Wang Weihao Xie Ying Liu Yuanhong Gao Hui Chang Department of Radiation oncology State Key Laboratory of Oncology in South ChinaGuangzhou 510060China Guangdong Provincial Clinical Research center for cancer Guangzhou 510060China Sun Yat-sen University cancer center Guangzhou 510060China Department of Pediatric oncology State Key Laboratory of Oncology in South ChinaGuangzhou 510060China

The prevalence of colorectal cancer(CRC) is increasing annually and metastasis is the principal cause of death in patients with CRC, with the liver being the most frequently affected site. Many studies have shown a strong interplay between the gut flora, particularly Fusobacterium nucleatum(F. nucleatum), Escherichia coli, and Bacteroides fragilis, and the development of gut tumors. Some strains can induce gut inflammation and produce toxins that directly harm gut epithelial cells, ultimately accelerating the onset and progression of CRC. However,little clinical evidence exists on the specific interplay between the gut microflora and colorectal cancer liver metastasis(CRLM). Some research showed the existence of viable F. nucleatum in distant metastasis of ***, gut microbiota products, such as lipopolysaccharides, sodium butyrate, and protein cathepsin K, were also found to affect the development of CRC. This article summarizes the mechanism and research status of the interplay between gut microflora and CRLM, discusses the importance of gut microflora in the treatment of CRLM, and proposes a new approach to understanding the mechanism of CRLM and potential treatments for the microbiome. It is anticipated that the gut microbiota will be a formidable therapeutic and prophylactic tool for treating and preventing CRLM.

关键词： Gut microbiota liver metastasis colorectal cancer

Emerging clinical relevance of microbiome in cancer:promising biomarkers and therapeutic targets

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Protein & Cell 2024年第4期15卷 239-260页

作者： Jia-Hao Dai Xi-Rong Tan Han Qiao Na Liu state key laboratory of oncology in south china Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and TherapyGuangdong Provincial Clinical Research Center for CancerSun Yat-sen University Cancer CenterGuangzhou 510050China

The profound influence of microbiota in cancer initiation and progression has been under the spotlight for years,leading to numerous researches on cancer microbiome entering clinical *** promising biomarkers and therapeutic targets,the critical involvement of microbiota in cancer clinical practice has been increasingly ***,recent progress in this field is *** describe the potential of tumor-associated microbiota as effective diagnostic and prognostic biomarkers,*** addition,we highlight the relationship between microbiota and the therapeutic efficacy,toxicity,or side effects of commonly utilized treatments for cancer,including chemotherapy,radiotherapy,and *** that microbial factors influence the cancer treatment outcome,we further summarize some dominating microbial interventions and discuss the hidden risks of these *** review aims to provide an overview of the applications and advancements of microbes in cancer clinical relevance.

关键词： microbiome cancer diagnosis prognosis therapy

Ultrasound-responsive spherical nucleic acid against c-Myc/PD-L1 to enhance anti-tumoral macrophages in triple-negative breast cancer progression

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Science china(Life Sciences) 2024年第4期67卷 698-710页

作者： Runtian Wang Gaigai Li Fangyan Gao Feng Xu Xintong Li Jian Zhang Jinbo Li Xiaoxiang Guan Department of oncology The First Affiliated Hospital of Nanjing Medical UniversityNanjing 210029China state key laboratory of Analytical Chemistry for Life Sciences Jiangsu Key Laboratory of Advanced Organic MaterialsSchool of Chemistry and Chemical EngineeringChemistry and Biomedicine Innovation Center(ChemBIC)Nanjing UniversityNanjing 210023China Department of Medical oncology Fudan University Shanghai Cancer CenterDepartment of OncologyShanghai Medical CollegeFudan UniversityShanghai 200032China Jiangsu key Lab of cancer Biomarkers Prevention and TreatmentCollaborative Innovation Center for Cancer Personalized MedicineNanjing Medical UniversityNanjing 211166China

Triple-negative breast cancer(TNBC)is the most challenging breast cancer subtype because of its aggressive behavior and limited therapeutic targets.c-Myc is hyperactivated in the majority of TNBC tissues,however,it has been considered an“undruggable”target due to its disordered ***,we developed an ultrasound-responsive spherical nucleic acid(SNA)against c-Myc and PD-L1 in *** is a self-assembled and carrier-free system composed of a hydrophilic small-interfering RNA(si RNA)shell and a hydrophobic core made of a peptide nucleic acid(PNA)-based antisense oligonucleotide(ASO)and a *** accomplished significant enrichment in the tumor by enhanced permeability and retention(EPR)effect,the controllable release of effective elements by ultrasound activation,and the combination of targeted therapy,immunotherapy and *** study demonstrated significant anti-tumoral effects in vitro and in *** cytometry showed an invigorated tumor microenvironment(TME)characterized by a significant alteration in the composition of tumor-associated macrophages(TAM)and decreased proportion of PD-1-positive(PD-1+)T effector cells after appropriate treatment of the ultrasound-responsive SNA(USNA).Further experiments verified that tumor-conditioned macrophages residing in the TME were transformed into the anti-tumoral *** finding offers a novel therapeutic strategy against the“undruggable”c-Myc,develops a new targeted therapy for c-Myc/PD-L1 and provides a treatment option for the TNBC.

关键词： triple-negative breast cancer c-Myc spherical nucleic acid self-assembly