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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

First-line penpulimab(an anti-PD1 antibody)and anlotinib(an angiogenesis inhibitor)with nab-paclitaxel/gemcitabine(PAAG)in metastatic pancreatic cancer:a prospective,multicentre,biomolecular exploratory,phase II trial

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Signal Transduction and Targeted Therapy 2024年第7期9卷 2960-2969页

作者： Huizi Sha Fan Tong Jiayao Ni Yi Sun Yahui Zhu Liang Qi Xiaoqin Li Wei Li Yan Yang Qing Gu Xing Zhang Xiaoxuan Wang Chan Zhu Dongsheng Chen Baorui Liu Juan Du The Comprehensive Cancer Center Nanjing Drum Tower HospitalAffiliated Hospital of Medical SchoolNanjing University&Clinical Cancer Institute of Nanjing UniversityNanjingChina The Comprehensive Cancer Center Nanjing Drum Tower HospitalClinical College of Traditional Chinese and Western MedicineNanjing University of Chinese MedicineNanjingChina Department of oncology The Affiliated Hospital of Jiangsu UniversityZhenjiangChina Department of oncology The First Affiliated Hospital of Soochow UniversitySuzhouChina Department of oncology The Affiliated Jiangning Hospital of Nanjing Medical UniversityNanjingChina National Institute of Healthcare Data Science at Nanjing University NanjingChina State Key Laboratory of Neurology and oncology Drug Development Jiangsu Simcere Diagnostics Co.Ltd.Nanjing Simcere Medical Laboratory Science Co.Ltd.NanjingChina

Metastatic pancreatic cancer(mPC)has a dismal ***,we conducted a prospective,multicentre,single-arm,phase II trial evaluating the efficacy and safety of penpulimab and anlotinib in combination with nab-paclitaxel/gemcitabine(PAAG)in patients with first-line mPC(NCT05493995).The primary endpoints included the objective response rate(ORR)and disease control rate(DCR),while secondary endpoints encompassed progression-free survival(PFS),overall survival(OS),and *** 66 patients analysed for efficacy,the best response,indicated by the ORR,was recorded at 50.0%(33/66)(95%CI,37.4–62.6%),with 33 patients achieving partial response(PR).Notably,the DCR was 95.5%(63/66,95%CI,87.3–99.1%).The median PFS(mPFS)and OS(mOS)were 8.8(95%CI,8.1–11.6),and 13.7(95%CI,12.4 to not reached)months,*** 3/4 treatment-related adverse events(TRAEs)were reported in 39.4%of patients(26/66).In prespecified exploratory analysis,patients with altered SWI/SNF complex had a poorer ***,low serum CA724 level,high T-cell recruitment,low Th17 cell recruitment,and high NK CD56dim cell scores at baseline were potential predicative biomarkers for more favourable *** conclusion,PAAG as a first-line therapy demonstrated tolerability with promising clinical efficacy for *** biomolecular findings identified in this study possess the potential to guide the precise clinical application of the triple-combo regimen.

关键词： CA724 prospective centre

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

Inetetamab combined with pyrotinib and oral vinorelbine for patients with human epidermal growth factor receptor 2 positive advanced breast cancer:A single-arm phase 2 clinical trial

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Cancer Pathogenesis and Therapy 2024年第1期2卷 31-37页

作者： Nan Jin Yi Xu Siqi Wang Chunxiao Sun Xueqi Yan Fan Yang Yan Liang Weiwei Chen Xiang Huang Department of oncology The First Affiliated Hospital of Nanjing Medical UniversityNanjingJiangsu 210029China Department of Pathology The First Affiliated Hospital of Nanjing Medical UniversityNanjingJiangsu 210029China Radiology Department The First Affiliated Hospital of Nanjing Medical UniversityNanjingJiangsu 210029China Department of oncology Affiliated Jinling HospitalMedical School of Nanjing UniversityNanjingJiangsu 210000China

Background Human epidermal growth factor receptor 2(HER2)-targeted agents have significantly improved the outcomes of patients with HER2-positive breast cancer;however,a large proportion of patients still develop resistance to *** this study,we investigated the efficacy and safety of inetetamab,another anti-HER2 antibody,combined with pyrotinib and oral vinorelbine in patients with HER2-positive advanced breast cancer so as to provide new ideas for the *** In this prospective,single-arm,phase 2 trial,patients with HER2-positive advanced breast cancer with disease progression after trastuzumab were *** received a combination of inetetamab(loading dose of 8 mg/kg and subsequent doses of 6 mg/kg intravenously once every 3 weeks),pyrotinib(400 mg orally once daily),and vinorelbine(60 mg/m^(2)orally once weekly)until disease progression or intolerable *** primary endpoint was progression-free survival(PFS).The secondary endpoints included objective response rate(ORR),overall survival(OS),disease control rate(DCR),and *** Between February 13,2022 and December 25,2022,30 patients were screened and enrolled in this *** median age of the patients at enrollment was 54 years,12 patients(40.0%)had hormone-receptor-positive disease and 23 patients(76.7%)had visceral *** median PFS was 8.63 months(95%confidence interval[CI]4.15-13.12 months).The median OS was not *** ORR was 53.3%(16/30)and the DCR was 96.7%(29/30).The most common Grade III/IV adverse events were leukopenia(n=5,16.7%),neutropenia(n=4,13.3%),and diarrhea(n=3,10%).No treatment-related serious adverse events or deaths *** The combination regimen of inetetamab,pyrotinib,and oral vinorelbine showed encouraging efficacy and favorable safety in patients with HER2-positive advanced breast cancer and could be considered as an alternative treatment option for the patients.

关键词： Human epidermal growth factor receptor 2 Breast cancer Inetetamab Pyrotinib Vinorelbine

ROR2 promotes invasion and chemoresistance of triple-negative breast cancer cells by activating PI3K/AKT/mTOR signaling

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oncology Research 2024年第7期32卷 1209-1219页

作者： XIA DA HAN GE JUNFENG SHI CHUNHUA ZHU GUOZHU WANG YUAN FANG JIN XU Department of Breast and Thyroid Nanjing First HospitalNanjing Medical UniversityNanjingChina Department of General Surgery The First Affiliated Hospital of Nanjing Medical UniversityNanjingChina Department of oncology Nanjing First HospitalNanjing Medical UniversityNanjingChina Department of Pathology Nanjing First HospitalNanjing Medical UniversityNanjingChina

Objective:This study aimed to investigate the role of receptor tyrosine kinase-like orphan receptor 2(ROR2)in triple-negative breast cancer(TNBC).Methods:ROR2 expression in primary TNBC and metastatic TNBC tissues was analyzed by immunohistochemical staining and ***2 expression in TNBC cell lines was detected by PCR and Western blot *** migration,invasion and chemosensitivity of TNBC cells with overexpression or knockdown of ROR2 were ***:ROR2 expression was high in metastatic TNBC ***2 knockdown suppressed the migration,invasion and chemoresistance of TNBC ***2 overexpression in MDA-MB-435 cells promoted the migration,invasion,and ***,ROR2 knockdown in HC1599 and MDA-MB-435 adriamycin-resistant cells enhanced chemosensitivity to ***2 could activate PI3K/AKT/mTOR signaling in TNBC ***:ROR2 is upregulated and promotes metastatic phenotypes of TNBC by activating PI3K/AKT/mTOR signaling.

关键词： Receptor tyrosine kinase-like orphan receptor 2 Triplet-negative breast cancer Proliferation Apoptosis PI3K/AKT/mTOR signaling Metastasis

Phase II study of novel orally PI3Kα/δinhibitor TQ-B3525 in relapsed and/or refractory follicular lymphoma

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Signal Transduction and Targeted Therapy 2024年第5期9卷 2193-2201页

作者： Huaqing Wang Jifeng Feng Yanyan Liu Zhengzi Qian Da Gao Xuehong Ran Hui Zhou Lihong Liu Binghua Wang Meiyun Fang Hebing Zhou Zhenqian Huang Shi Tao Zhuowen Chen Liping Su Hang Su Yu Yang Xiaobao Xie Huijing Wu Ping Sun Guoyu Hu Aibin Liang Zhiming Li Department of oncology Tianjin Union Medical Center of Nankai UniversityTianjin 300121PR China The Institute of Translational Medicine Tianjin Union Medical Center of Nankai UniversityTianjin 300121PR China Department of medical oncology Jiangsu Cancer HospitalThe Affiliated Cancer Hospital of Nanjing Medical UniversityNanjing 210009PR China Department of medical oncology Henan Cancer HospitalThe Affiliated Cancer Hospital of Zhengzhou UniversityZhengzhou 450003PR China Department of medical oncology Tianjin Medical University Cancer Institute and HospitalTianjin 300060PR China Department of Hematology The Affiliated Hospital of Inner Mongolia Medical College010050 HohhotPR China Department of Hematology Weifang People’s HospitalThe First Affiliated Hospital of Weifang Medical University261000 WeifangPR China Department of Lymphoma&Hematology Hunan Cancer HospitalThe Affiliated Cancer Hospital of Xiangya School of MedicineCentral South University410013 ChangshaPR China Department of Hematology The Fourth Hospital of Hebei Medical University and Hebei Tumor Hospital050011 ShijiazhuangPR China Department of Lymphoma Weihai Central Hospital264400 WeihaiPR China Department of Hematology and Rheumatology The Affiliated Zhongshan Hospital of Dalian University116001 DalianPR China Department of Hematology Beijing Luhe Hospital101199 BeijingPR China Department of Hematology The First Affiliated Hospital of Guangzhou Medical University510120 GuangzhouPR China Department of Hematology The First Affiliated Hospital of Hainan Medical College570102 HaikouPR China Department of Hematology The First People’s Hospital of Foshan528000 FoshanPR China Department of Hematology Shanxi Cancer Hospital030013 TaiyuanPR China Department of Lymphoma Senior Department of HematologyThe Fifth Medical Center of Chinese PLA General Hospital100039 BeijingPR China Department of Lymphoma and Head and Neck Cancer Fujian Cancer Hospital350014 FuzhouPR China Department of Hematology The First People’s Hospit

This registration study assessed clinical outcomes of TQ-B3525,the dual phosphatidylinositol-3-kinase(PI3K)α/δinhibitor,in relapsed and/or refractory follicular lymphoma(R/R FL).This phase II study(*** *** March 27,2020)comprised run-in stage and stage 2.R/R FL patients after≥2 lines therapies received oral 20 mg TQ-B3525 once daily in a 28-day cycle until intolerable toxicity or disease *** endpoint was independent review committee(IRC)-assessed objective response rate(ORR).Based on results(ORR,88.0%;duration of response[DOR],11.8 months;progression-free survival[PFS],12.0 months)in 25 patients at run-in stage,second stage study was initiated and included 82 patients for efficacy/safety *** received prior-line(median,3)therapies,with 56.1%refractory to previous last therapies;73.2%experienced POD24 at *** stage 2,ORR was 86.6%(71/82;95%CI,77.3-93.1%),with 28(34.2%)complete *** control rate was 95.1%due to 7(8.5%)stable *** time to response was 1.8 *** 71 responders,median DOR was not reached;18-month DOR rate was 51.6%.with median follow-up of 13.3 months,median PFS was 18.5(95%CI,10.2-not estimable)*** overall survival(OS)was not reached by cutoff date;24-month OS rate was estimated as 86.1%.Response rates and survival data were consistent across all *** 3 or higher treatment-related adverse events were observed in 63(76.8%)cases,with neutropenia(22.0%),hyperglycemia(19.5%),and diarrhea(13.4%)being ***-B3525 showed favorable efficacy and safety for R/R FL patients after≥2 lines prior therapies.

关键词： lymphoma assessed initiated

Uncovering the epidemiology of bladder cancer in the Arab world: A review of risk factors, molecular mechanisms, and clinical features

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Asian Journal of Urology 2024年第3期11卷 406-422页

作者： Noura F.Abbas Marc R.Aoude Hampig R.Kourie Humaid OAl-Shamsi Department of Hematology-oncology Hotel Dieu De France HospitalSaint Joseph University of BeirutRiad El SolhLebanon Department of oncology Burjeel Cancer InstituteBurjeel Medical CityAbu DhabiUnited Arab Emirates Innovation and Research Center Burjeel Cancer InstituteBurjeel Medical CityAbu DhabiUnited Arab Emirates College of Medicine University of SharjahSharjahUnited Arab Emirates Emirates oncology Society DubaiUnited Arab Emirates College of Medicine Gulf Medical UniversityAjmanUnited Arab Emirates

Objective:Bladder cancer(BC)is a significant public health concern in the Middle East and North Africa,but the epidemiology and clinicopathology of the disease and contributors to high mortality in this region remain poorly *** aim of this systematic review was to investigate the epidemiological features of BC in the Arab world and compare them to those in Western countries in order to improve the management of this ***:An extensive electronic search of the PubMed/PMC and Cochrane Library databases was conducted to identify all articles published until May 2022,following the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines.A total of 95 articles were included in the final analysis after title,abstract,and full-text screening,with additional data obtained from the GLOBOCAN and WHO 2020 databases.

关键词： Bladder cancer Epidemiology Risk factor Biomarker Schistosomiasis Arab world Urology

Current status and trends in small nucleic acid drug development:Leading the future

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Acta Pharmaceutica Sinica B 2024年第9期14卷 3802-3817页

作者： Yuxi Miao Chen Fu Zhaojin Yu Lifeng Yu Yu Tang Minjie Wei Department of Pharmacology School of PharmacyChina Medical UniversityShenyang 110122China Liaoning Key Laboratory of Molecular Targeted Anti-Tumor Drug Development and Evaluation China Medical UniversityShenyang 110122China Liaoning medical Diagnosis and Treatment Center Shenyang 110000China Department of oncology Cancer Hospital of China Medical UniversityLiaoning Cancer Hospital and InstituteShenyang 110042China

Small nucleic acid drugs,composed of nucleotides,represent a novel class of pharmaceuticals that differ significantly from conventional small molecule and antibody-based *** agents function by selectively targeting specific genes or their corresponding messenger RNAs(mRNAs),further modulating gene expression and regulating translation-related *** examples within this category include antisense oligonucleotides(ASO),small interfering RNAs(siRNAs),micro-RNAs(miRNAs),and *** emergence of small nucleic acid drugs as a focal point in contemporary biopharmaceutical research is attributed to their remarkable specificity,facile design,abbreviated development cycles,expansive target spectrum,and prolonged *** challenges such as poor stability,immunogenicity,and permeability issues have been addressed through the integration of chemical modifications and the development of drug delivery *** review provides an overview of the current status and prospective trends in small nucleic acid drug *** with a historical context,we introduce the primary classifications and mechanisms of small nucleic acid ***,we delve into the advantages of the *** and Drug Administration(FDA)approved drugs and mainly discuss the challenges encountered during their *** from researching chemical modification and delivery system that efficiently deliver and enrich small nucleic acid drugs to target tissues,promoting endosomal escape is a critical scientific question and important research direction in siRNA drug *** directions in this field will prioritize addressing these challenges to facilitate the clinical transformation of small nucleic acid drugs.

关键词： Small nucleic acid drugs Oligonucleotide drugs siRNA ASO miRNA Aptamer RNAi Drug development

Syrosingopine,an anti-hypertensive drug and lactate transporter(MCT1/4)inhibitor,activates hepatic stellate cells and exacerbates liver fibrosis in a mouse model

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Genes & Diseases 2024年第4期11卷 28-30页

作者： Meichun Guo Yannian Gou Xiangyu Dong Jiamin Zhong Aohua Li Ailing Hao Tongchuan He Jiaming Fan Ministry of Education Key Laboratory of Diagnostic Medicine and the School of Laboratory Diagnostic MedicineChongqing Medical UniversityChongqing 400016China Molecular oncology Laboratory Department of Orthopaedic Surgery and Rehabilitation MedicineThe University of Chicago Medical CenterChicagoIL 60637USA

Syrosingopine is an anti-hypertensive drug and can cause high intracellular lactate levels and end-product inhibition of lactate dehydrogenase by inhibiting the lactate transporters MCT1 and *** studies have shown that syrosingopine plays an essential role in the process of glycolytic blockade,ATP depletion,and cell death in cancer due to high intracellular levels of lactate.

关键词： hypertensive MCT1 drug