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Improving the value of molecular testing:current status and opportunities in colorectal Cancer Precision Medicine

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cancer Biology & medicine 2024年第1期21卷 21-28页

作者： Haiyun Li Linwei Guo Chenchen Wang Xin Hu Ye Xu Department of Colorectal Surgery Fudan University Shanghai Cancer CenterShanghai 200032China Department of Oncology Shanghai Medical CollegeFudan UniversityShanghai 200032China Department of Gastrointestinal Medical Oncology Fudan University Shanghai Cancer CenterShanghai 200032China precision cancer Medical Center Affiliated with Fudan University Shanghai cancer Center Shanghai 201315China

Colorectal cancer(CRC)is the second leading cause of cancer-related deaths worldwide1.Surgical radical resection with adjuvant chemotherapy remains the primary treatment choice for CRC,but the 5-year postoperative survival rate is only approximately 60%,and approximately one-third of patients with CRC experience recurrence within 2 years of surgery2.Fortunately,the transformation of high-throughput sequencing has accelerated the development of precision medicine.For example,KRAS mutations indicate resistance to anti-epidermal growth factor receptor(EGFR)-targeted therapies in CRC3.Furthermore,molecular-guided individualized therapy has brought new promise in major clinical areas and challenges,such as novel biomarkers predicting sensitivity and resistance to immunotherapy for microsatellite stable(MSS)CRC.

关键词： cancer chemotherapy colorectal

Cancer Precision Medicine in China

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Genomics, Proteomics & Bioinformatics 2016年第5期14卷 325-328页

作者： Hui Li National Clinical Research Center for cancer(Tianjin) Tianjin 300060China Department of Gastrointestinal cancer Biology Tianjin Medical University Cancer Institute&HospitalTianjin 300060China

Background cancer, as a global health issue, has been attracting increasing attention from scientists, medical professionals, as well as the general population. During the past several decades, many therapeutic approaches, including surgery, chemotherapy, radiotherapy and immunotherapy, have come into play for cancer treatment. Nonetheless, many of these treatments are not personalized according to the specific situation or genetic context of a particular patient. Nowadays, precision medicine,

关键词： Cancer Precision Medicine in China

Application of next-generation sequencing technology to precision medicine in cancer: joint consensus of the Tumor Biomarker Committee of the Chinese Society of Clinical Oncology

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cancer Biology & medicine 2019年第1期16卷 189-204页

作者： Xuchao Zhang Zhiyong Liang Shengyue Wang Shun Lu Yong Song Ying Cheng Jianming Ying Weiping Liu Yingyong Hou Yangqiu Li Yi Liu Jun Hou Xiufeng Liu Jianyong Shao Yanhong Tai Zheng Wang Li Fu Hui Li Xiaojun Zhou Hua Bai Mengzhao Wang You Lu Jinji Yang Wenzhao Zhong Qing Zhou Xuening Yang Jie Wang Cheng Huang Xiaoqing Liu Xiaoyan Zhou Shirong Zhang Hongxia Tian Yu Chen Ruibao Ren Ning Liao Chunyan Wu Zhongzheng Zhu Hongming Pan Yanhong Gu Liwei Wang Yunpeng Liu Suzhan Zhang Tianshu Liu Gong Chen Zhimin Shao Binghe Xu Qingyuan Zhang Ruihua Xu Lin Shen Yilong Wu Guangdong Lung cancer Institute Medical Research Center Cancer Center of Guangdong Provincial People's Hospital and Guangdong Academy of Medical Sciences Affiliated Guangdong Provincial People's Hospital South China University of Technology Department of Pathology Peking Union Medical College Hospital Chinese Academy of Medical Sciences National Research Center for Translational medicine Shanghai Rui Jin Hospital Shanghai Jiao Tong University School of Medicine Lung Tumor Clinical Medical Center Shanghai Chest Hospital Shanghai Jiao Tong University Division of Respiratory medicine Jinling Hospital Nanjing University School of Medicine Department of Oncology Jilin Cancer Hospital Department of Pathology National Cancer Center/Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Department of Pathology West China Hospital Sichuan University Department of Pathology Zhongshan Hospital Fudan University Department of Hematology First Affiliated Hospital Institute of Hematology School of Medicine Jinan University Laboratory of Oncology Affiliated Hospital of the Academy of Military Medical Sciences Department of Oncology First Clinical College of South China University of Technology/Guangdong Lung Cancer Institute People's Liberation Army cancer Center of Bayi Hospital Affiliated to Nanjing University of Chinese medicine Department of Pathology Sun Yat-sen University Cancer Center Department of Pathology Affiliated Hospital of the Academy of Military Medical Sciences Department of Pathology Beijing Hospital Department of Breast cancer Pathology and Research Laboratory of cancer Tianjin Medical University Cancer Institute and Hospital National Clinical Research Center for Cancer Key Laboratory of Cancer Prevention and Therapy Tianjin Tianjin’s Clinical Research Center for Cancer Department of Pathology Jinling Hospital Nanjing University School of Medicine State Key Laboratory of Molecular Oncology Department of Medical Oncology National Cancer Center/Canc

Next-generation sequencing(NGS) technology is capable of sequencing millions or billions of DNA molecules simultaneously.Therefore, it represents a promising tool for the analysis of molecular targets for the initial diagnosis of disease, monitoring of disease progression, and identifying the mechanism of drug resistance. On behalf of the Tumor Biomarker Committee of the Chinese Society of Clinical Oncology(CSCO) and the China Actionable Genome Consortium(CAGC), the present expert group hereby proposes advisory guidelines on clinical applications of NGS technology for the analysis of cancer driver genes for precision cancer therapy. This group comprises an assembly of laboratory cancer geneticists, clinical oncologists, bioinformaticians,pathologists, and other professionals. After multiple rounds of discussions and revisions, the expert group has reached a preliminary consensus on the need of NGS in clinical diagnosis, its regulation, and compliance standards in clinical sample collection. Moreover, it has prepared NGS criteria, the sequencing standard operation procedure(SOP), data analysis, report, and NGS platform certification and validation.

关键词： Next-generation sequencing technology cancer consensus

The heterogeneous immune landscape between lung adenocarcinoma and squamous carcinoma revealed by single-cell RNA sequencing

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Signal Transduction and Targeted Therapy 2022年第9期7卷 3567-3583页

作者： Chengdi Wang Qiuxiao Yu Tingting Song Zhoufeng Wang Lujia Song Ying Yang Jun Shao Jingwei Li Yinyun Ni Ningning Chao Li Zhang Weimin Li Department of Respiratory and Critical Care medicine Med-X Center for ManufacturingCenter of Precision MedicinePrecision Medicine Key Laboratory of Sichuan ProvinceFrontiers Science Center for Disease-related Molecular NetworkWest China HospitalWest China Medical SchoolSichuan University610041 ChengduChina National cancer Center National Clinical Research Center for CancerCancer Hospital&Shenzhen HospitalChinese Academy of Medical Sciences and Peking Union Medical College518116ShenzhenChina

A thorough interrogation of the immune landscape is crucial for immunotherapy strategy selection and prediction of clinical responses in non-small-cell lung cancer(NSCLC)patients.Single-cell RNA sequencing(scRNA-seq)techniques have prompted the opportunity to dissect the distinct immune signatures between lung adenocarcinoma(LUAD)and lung squamous cell carcinoma(LUSC),the two major subtypes of NSCLC.Here,we performed scRNA-seq on 72,475 immune cells from 40 samples of tumor and matched adjacent normal tissues spanning 19 NSCLC patients,and drew a systematic immune cell transcriptome atlas.Joint analyses of the distinct cellular compositions,differentilly expressed genes(DEGs),cell-cell interactions,pseudotime trajectory,transcriptomic factors and prognostic factors based on The cancer Genome Atlas(TCGA),revealed the central roles of cytotoxic and effector T and NK cells and the distinct functional macrophages(Mo)subtypes in the immune microenvironment heterogeneity between LUAD and LUSC.The dominant subtype of Mo was FABP4-Mp in LUAD and SPP1-Mo in LUSC.Importantly,we identifieda novel lymphocyte-related Mo cluster,which we named SELENOP-Mo,and further established its antitumor role in both types,especially in LUAD.Our comprehensive depiction of the immune heterogeneity and definition of Mp clusters could help design personalized treatment for lung cancer patients in clinical practice.

关键词： lung squamous adenocarcinoma

Etiological roles of core promoter variation in triple-negative breast cancer

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Genes & Diseases 2023年第1期10卷 228-238页

作者： Teng Huang Jiaheng Li San Ming Wang cancer Centre and Institute of Translational medicine Faculty of Health SciencesMinistry of Education Frontiers Science Center for Precision OncologyUniversity of MacaoTaipaMacao SAR 999078China

Abnormal geneexpression playskeyrole in cancerdevelopment.Acorepromoter is located around the transcriptional start site.Through interaction between core promoter sequences and transcriptional factors,core promoter controls transcriptional initiation.We hypothesized that in cancer,core promoter sequences could be mutated to interfere the interaction with transcriptional factors,resulting in altered transcriptional initiation and abnormal gene expression and cancer development.We used triple-negative breast cancer(TNBC)as a model to test our hypothesis.We collected genome-wide core promoter variants from 279 TNBC genomes.After extensive filtering of normal genomic polymorphism,we identified 19,427 recurrent somatic variants in 1,238 core promoters of 1,274 genes and 1,694 recurrent germline variants in 272 core promoters of 294 genes.Many of the affected genes were oncogenes and tumor suppressors.Analysis of RNA-seq data from the same patient cohort identified increased or decreased gene expression in 439 somatic and 85 germline variantsaffected genes,and the results were validated by luciferase reporter assay.By comparing with the core promoter variation data from 610 unclassified breast cancer,we observed that core promoter variants in TNBC were highly TNBC-specific.We further identified the drugs targeting the genes with core promoter variation.Our study demonstrates that core promoter is highly mutable in cancer,and can play etiological roles in TNBC and other types of cancer through influencing transcriptional initiation.

关键词： Core promoter RNA-seq Triple-negative breast cancer Variation Whole exome sequencing

Research advances of secretory proteins in malignant tumors

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Chinese Journal of cancer Research 2021年第1期33卷 115-132页

作者： Na Zhang Jiajie Hao Yan Cai Mingrong Wang State Key Laboratory of Molecular Oncology Center for Cancer Precision MedicineNational Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China

Secretory proteins in tumor tissues are important components of the tumor microenvironment.Secretory proteins act on tumor cells or stromal cells or mediate interactions between tumor cells and stromal cells,thereby affecting tumor progression and clinical treatment efficacy.In this paper,recent research advances in secretory proteins in malignant tumors are reviewed.

关键词： Secretory protein tumor microenvironment stromal cells tumor progression drug resistance

Meeting abstracts of Colossal Facet Conference-3rd World Congress on cancer 2019“New strategies to prevent,diagnose and treat cancer based on precision medicine”

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Journal of cancer Metastasis and Treatment 2020年第1期6卷 17-54页

作者： [Anonymous] Journal of cancer Metastasis and Treatment Editorial Office

Editorial Note This special issue of Journal of cancer Metastasis and Treatment is dedicated to the proceedings of the 3rd World Congress on cancer 2019 held in Prague(Czech Republic)during September 23-25(http://***/... 详细信息

关键词： cancer medicine World

Impaired Hypothalamic Regulation of Sympathetic Outflow in Primary Hypertension

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Neuroscience Bulletin 2019年第1期35卷 124-132页

作者： Jing-Jing Zhou Hui-Jie Ma Jian-Ying Shao Hui-Lin Pan De-Pei Li Division of Anesthesiology and Critical Care The University of Texas MD Anderson Cancer Center Department of Physiology Hebei Medical University Department of medicine Center for Precision MedicineUniversity of Missouri

The hypothalamic paraventricular nucleus(PVN) is a crucial region involved in maintaining homeostasis through the regulation of cardiovascular, neuroendocrine, and other functions. The PVN provides a dominant source of excitatory drive to the sympathetic outflow through innervation of the brainstem and spinal cord in hypertension. We discuss current findings on the role of the PVN in the regulation of sympathetic output in both normotensive and hypertensive conditions. The PVN seems to play a major role in generating the elevated sympathetic vasomotor activity that is characteristic of multiple forms of hypertension, including primary hypertension in humans. Recent studies in the spontaneously hypertensive rat model have revealed an imbalance of inhibitory and excitatory synaptic inputs to PVN presympathetic neurons as indicated by impaired inhibitory and enhanced excitatory synaptic inputs in hypertension.This imbalance of inhibitory and excitatory synaptic inputs in the PVN forms the basis for elevated sympathetic outflow in hypertension. In this review, we discuss the disruption of balance between glutamatergic and GABAergic inputs and the associated cellular and molecular alterations as mechanisms underlying the hyperactivity of PVN pre-sympathetic neurons in hypertension.

关键词： Hypothalamus Paraventricular nucleus Synaptic plasticity Essential hypertension Sympathetic nervous system

Monoacylglycerol lipase inhibitors: modulators for lipid metabolism in cancer malignancy,neurological and metabolic disorders

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Acta Pharmaceutica Sinica B 2020年第4期10卷 582-602页

作者： Hui Deng Weimin Li precision medicine Key Laboratory of Sichuan Province&precision medicine Center West China HospitalSichuan UniversityChengdu 610041China

Monoacylglycerol lipase(MAGL)is a serine hydrolase that plays a crucial role catalysing the hydrolysis of monoglycerides into glycerol and fatty acids.It links the endocannabinoid and eicosanoid systems together by degradation of the abundant endocannabinoid 2-arachidaoylglycerol into arachidonic acid,the precursor of prostaglandins and other inflammatory mediators.MAGL inhibitors have been considered as important agents in many therapeutic fields,including anti-nociceptive,anxiolytic,antiinflammatory,and even anti-cancer.Currently,ABX-1431,a first-in-class inhibitor of MAGL,is entering clinical phase 2 studies for neurological disorders and other diseases.This review summarizes the diverse(patho)physiological roles of MAGL and will provide an overview on the development of MAGL inhibitors.Although a large number of MAGL inhibitors have been reported,novel inhibitors are still required,particularly reversible ones.

关键词： Monoacylglycerol lipases 2-Arachidaoylglycerol Arachidonic acid Drug discovery cancer Neuroinflammation Metabolic syndrome