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ZNF582 hypermethylation promotes metastasis of nasopharyngeal carcinoma by regulating the transcription of adhesion molecules Nectin-3 and NRXN3

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Cancer Communications 2020年第12期40卷 721-737页

作者： Yin Zhao Xiao-Hong Hong Kang Li Ying-Qing Li Ying-Qin Li Shi-Wei He Pan-Pan Zhang Jun-Yan Li Qian Li Ye-Lin Liang Yang Chen Jun Ma Na Liu Yu-Pei Chen Experimental Research Department Sun Yat-sen University Cancer CenterState Key Laboratory of Oncology in South ChinaCollaborative Innovation Center of Cancer MedicineGuangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and TherapyGuangzhouGuangdong 510060P.R.China Center for Translational Medicine The First Affiliated HospitalSun Yat-sen UniversityGuangzhouGuangdong 510080P.R.China

Background:Epigenetic regulation plays an important role in the development and progression of nasopharyngeal carcinoma(NPC).However,the epigenetic mechanisms underlying NPC metastasis remains poorly *** aimed to find functional genes which regulate the metastasis of NPC and identify therapeutic targets for NPC ***:Bisulfite pyrosequencing was used to analyze zinc finger protein 582(ZNF582)methylation in NPC tissues and cell *** reverse transcription-polymerase chain reaction(qRT-PCR)and Western blotting were used to determine the expression of *** vitro and in vivo experiments were performed to evaluate the biological function of ZNF582 in ***582-targeting genes were identified by chromatin immunoprecipitation sequencing(ChIP-seq)and were confirmed by ChIP-qPCR and luciferase ***:ZNF582 promoter was hypermethylated in NPC,and both the mRNA and protein levels of ZNF582 were down-regulated in NPC tissues and cell *** restoration of ZNF582 inhibited NPC migration,invasion,and metastasis,while the knockdown of ZNF582 promoted NPC migration,invasion,and metastasis in vitro and in ***582 directly regulated the transcription and expression of adhesion molecules Nectin-3 and *** Nectin-3 and NRXN3 were identified as functional targets of ZNF582,and the restoration or abrogation of these genes reversed the tumor suppressor effect of ZNF582 in NPC ***:ZNF582 acts as a tumor suppressor gene in NPC by regulating the transcription and expression of adhesion molecules Nectin-3 and NRXN3,which may provide novel therapeutic targets for NPC treatment.

关键词： Metastasis Nasopharyngeal carcinoma Nectin-3 NRXN3 ZNF582

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A Phase Ⅱ Trial of Gefitinib as Maintenance Therapy after First-Line Chemotherapy for Advanced Non-Small Cell Lung Cancer in China

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Chinese Journal of Cancer Research 2010年第1期22卷 1-9页

作者： Lu Yang Zhi-jie Wang Tong-tong An Hua Bai Jun Zhao Jian-chun Duan Ping-ping Li Mei-na Wu Hong Sun Li Liang Jie Wang The key laboratory of Carcinogenesis and Translational Research （Ministry of EducationDepartment of thoracic Medical oncology Department of Traditional Chinese Medicine Combined West Medical oncology Peking University School of Oncology Beijing Cancer Hospital ＆ Institute Beijing 100142 China Department of oncology the Third Hospital of Peking University Beijing 100083 China

Objective： To investigate the efficacy and safety of gefitinib as maintenance therapy for advanced non-small cell lung cancer （NSCLC） patients who obtained disease control （DC） after first-line chemotherapy in Chinese population. Methods： Chinese patients with advanced NSCLC treated with standard chemotherapy and obtained DC were assigned to receive gefitinib as maintenance treatment. The primary end point was overall survival time （OS）, the second end point was disease control rate （DCR） and progression-free survival time （PFS）. DCR included complete response （CR） plus partial response （PR） and plus stable disease （SD）. The impact of epidermal growth factor receptor （EGFR） mutation status on the treatment as exploratory point was also evaluated by denaturing high-performance liquid chromatography （DHPLC）. Results： Among 75 enrolled patients, the overall response rate was 37% and the DCR （CR ＋ PR ＋SD） was 66%. The median PFS and OS were 17.13 months and 26.13 months respectively, with 1- and 2-year survival rates 89.3% and 34.7%. Patients harboring somatic EGFR mutations obtained a prolonged median PFS and OS compared with EGFR wide type （25.1 vs. 13.0 months, P=0.019 and 33.37 vs. 25.57 months, P=0.014, respectively）. In COX regression model, only EGFR mutation status was the independently factor influencing both PFS and OS （P=0.029 and 0.017, respectively）, however, rash status was the predictor in terms of PFS （P=0.027）. Conclusion： Gefitinib produced encouraging survival when delivered as maintenance therapy in Chinese patients obtaining DC after first-line chemotherapy, especially for patients carrying somatic EGFR mutations. EGFR mutation is an independently predictive factor of survival.

关键词： Gefitinib Maintenance therapy Non-small cell lung cancer

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Anlotinib suppresses lymphangiogenesis and lymphatic metastasis in lung adenocarcinoma through a process potentially involving VEGFR-3 signaling

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Cancer Biology & Medicine 2020年第3期17卷 753-767页

作者： Tingting Qin Zhujun Liu Jing Wang Junling Xia Shaochuan Liu Yanan Jia Hailin Liu Kai Li Department of thoracic oncology Tianjin Medical University Cancer Institute and HospitalNational Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjinTianjin's Clinical Research Center for CancerTianjin 300060China Department of Biomedical Engineering Tianjin Medical UniversityTianjin 300070China

Objective:Lymphatic metastasis is one of the leading causes of malignancy dispersion in various types of ***,few anti-lymphangiogenic drugs have been approved for clinical use to ***,new therapies to block lymphangiogenesis are urgently ***:Immunohistochemistry,immunofluorescence,Western blot,migration assays,and lymphangiogenesis and lymphatic metastasis assays were ***:Anlotinib,a receptor tyrosine kinase inhibitor,suppressed the rate of new metastatic lesions(31.82%in the placebo arm and 18.18%in the anlotinib arm)in patients with advanced lung adenocarcinoma who were enrolled in our ALTER-0303 study.D2-40+-lymphatic vessel density was strongly correlated with disease stage,metastasis,and poor prognosis in 144 Chinese patients with lung *** mice bearing A549EGFP tumors,tumor lymphatic vessel density,tumor cell migration to lymph nodes,and the number of distant metastatic lesions were lower in the anlotinib group than in the *** inhibited the growth and migration of human lymphatic endothelial cells(hLECs)and lymphangiogenesisin vitro andin *** of hLECs with anlotinib downregulated phosphorylated vascular endothelial growth factor receptor 3(VEGFR-3).Conclusions:Anlotinib inhibits lymphangiogenesis and lymphatic metastasis,probably through inactivating VEGFR-3 *** results indicate that anlotinib may be beneficial for treatment in avoiding lymphangiogenesis and distant lymphatic metastasis in lung adenocarcinoma.(Trial registration:ALTER0303;NCT02388919;March 17,2015.)

关键词： Anlotinib VEGFR-3 dephosphorylation lymphangiogenesis lymph node metastasis lung adenocarcinoma

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Co-delivery of doxorubicin and curcumin via cRGD-peptide modified PEG-PLA self-assembly nanomicelles for lung cancer therapy

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Chinese Chemical Letters 2022年第5期33卷 2507-2511页

作者： Yunchu Zhang Tingting Li Yuzhu Hu Jing Chen Yihong He Xiang Gao Yan Zhang Department of thoracic oncology Cancer CenterState Key Laboratory of BiotherapyWest China HospitalWest China Medical SchoolSichuan University and Collaborative Innovation Center for BiotherapyChengdu 610041China Department of Neurosurgery and Institute of Neurosurgery State Key Laboratory of Biotherapy and Cancer CenterWest China HospitalWest China Medical SchoolSichuan University and Collaborative Innovation Center for BiotherapyChengdu 610041China

Lung cancer is the most common malignancy in the world, with a high mortality rate. Nevertheless,therapies to act effectively against lung cancer remain elusive. So far, chemotherapy is still the frontline treatment of lung cancer. Doxorubicin(DOX) is a broad-spectrum anti-tumor drug. However, DOX often has serious side effects and causes multi-drug resistance, which greatly limits its clinical *** this work, biodegradable methoxy poly(ethylene glycol)-poly(lactic acid)(MPEG-PLA) and cyclo(ArgGly-Asp-D-Phe-Lys)(c RGD) polypeptide modified PEG-PLA(c RGD-PEG-PLA) copolymers were used for the co-delivery of curcumin(CUR) and DOX(CUR-DOX/c RGD-M). The particle size of the self-assembled drugloaded nanomicelle approximately was 27.4 nm and the zeta potential was -2.7mV. Interestingly, CUR can enhance the uptake of DOX by Lewis lung carcinoma(LL/2) cells. The experimental results in vivo and in vitro showed that CUR-DOX/c RGD-M combination therapy could promote apoptosis of lung cancer cells, and conspicuously inhibit the tumor growth. Our data indicate that CUR-DOX/c RGD-M will be biodegradable and sustainable, which may have potential clinical application value in the treatment of lung cancer.

关键词： Doxorubicin Curcumin Lung cancer Nanomicelle Co-delivery

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Disseminated tumor cells in bone marrow as predictive classifiers for small cell lung cancer patients

Journal of the National Cancer Center

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Journal of the National Cancer Center 2024年第4期4卷 335-345页

作者： Ying Wang Jingying Nong Baohua Lu Yuan Gao Mingming Hu Cen Chen Lina Zhang Jinjing Tan Xiaomei Yang Peter Ping Lin Xingsheng Hu Tongmei Zhang Department of Medical oncology Beijing Chest HospitalCapital Medical UniversityBeijing Tuberculosis and Thoracic Tumor Research InstituteBeijingChina Department of thoracic Surgery Xuanwu HospitalCapital Medical UniversityBeijingChina The First School of Clinical Medicine Shaanxi University of Chinese MedicineXianyangChina Department of Cancer Research Center Beijing Chest HospitalCapital Medical UniversityBeijing Tuberculosis and Thoracic Tumor Research InstituteBeijingChina Beijing key laboratory for Tumor Invasion and Metastasis Department of Biochemistry and Molecular BiologyCapital Medical UniversityBeijingChina Joint laboratory for Precision diagnosis and treatment Translational Research in Malignant Tumors Gynecologic Oncology Basic and Clinical Research LaboratoryCapital Medical UniversityBeijingChina Cytelligen San DiegoUSA Department of Medical oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijingChina laboratory for Clinical Medicine Capital Medical UniversityBeijingChina

Background: Small cell lung cancer (SCLC) is a highly aggressive disease characterized by early metastasis. Ane- uploid CD31- disseminated tumor cells (DTCs) and CD31+ disseminated tumor endothelial cells (DTECs) residing in the bone marrow are generally considered as the initiators of metastatic process. However, the clinical signifi- cance of DTCs and DTECs in SCLC remains poorly understood. The aim of this study is to investigate the clinical implications of diverse subtypes of highly heterogeneous DTCs and DTECs in SCLC patients. Methods: Subtraction enrichment and immunostaining-fluorescence in situ hybridization (SE-iFISH) was applied to enrich and perform comprehensive morphologic, karyotypic, and phenotypic characterization of aneuploid DTCs and DTECs in 30 patients. Additionally, co-detection of circulating tumor cells (CTCs) and circulating tumor endothelial cells (CTECs) was conducted on 24 of the enrolled patients. Proof-of-concept of the whole exon sequencings (WES) on precisely selected different subtypes of CTCs or DTCs, longitudinally detected from a representative case with pathologically confirmed bone marrow metastasis, was validated to feasibly reveal genetic mutations in these cells. Results: DTCs, DTECs and their subtypes were readily detectable in SCLC patients. Comparative analysis re- vealed that the number of DTCs and DTECs was significantly higher than that of their corresponding CTCs and CTECs ( P treatment DTCs isolated

关键词： Bone marrow Aneuploid DTCs and DTECs SE-iFISH Prognosis SCLC

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Postoperative radiotherapy for thymus salivary gland carcinoma:A case report

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World Journal of Clinical Cases 2022年第26期10卷 9484-9492页

作者： Rui Deng Nan-Jing Li Liang-Liang Bai Shi-Hong Nie Xiao-Wen Sun Yong-Sheng Wang Clinical Trial Center National Medical Products Administration Key Laboratory for Clinical Research and Evaluation of Innovative DrugsDepartment of Thoracic OncologyWest China HospitalSichuan UniversityCheng Du 610041Sichuan ProvinceChina Department of Radiation oncology Cancer CenterWest China HospitalSichuan UniversityCheng Du 610041Sichuan ProvinceChina

BACKGROUND Salivary gland cancer is a rare disease in which cancer cells form in the tissues of the salivary *** mostly occurs in the glands that have secretion functions,such as the parotid gland,sublingual gland and submandibular *** is very rare when it occurs in other nonsecreting ***,we report one case of salivary gland carcinoma occurring in the thymus and discuss related diagnoses and treatment *** SUMMARY One 33-year-old middle-aged man presented with a thymus mass without any clinical symptoms when he underwent regular physical ***,the patient was admitted to the hospital for further *** tomography(CT)showed that there was a mass of 3 cm×2.8 cm×1.5 cm in the thymus *** patient had no symptom of discomfort or tumor-related medical history *** completing the preoperative examinations,it was confirmed that the patient had indications for *** surgeon performed a transthoracoscope"thymectomy+pleural mucostomy"for *** the operation,the tumor tissue was quickly frozen,and the symptomatic section showed a malignant *** final pathological result suggested thymus salivary gland carcinoma-mucoepidermoid carcinoma(MEC).In the second month after surgery,we performed local area radiotherapy for the patient,with a total radiation dose of 50.4 Gy/*** 12 mo of surgery,the patient underwent positron emission tomography-CT examination,which indicated that there was no sign of tumor recurrence or *** 16 mo of operation,CT scan re-examination showed that there was no sign of tumor recurrence or *** of the time of publication,the patient was followed up for one and a half *** had no sign of tumor recurrence and continued to *** The incidence of MEC in the thymus is low,and its diagnosis needs to be combined with clinical features and imaging *** analysis plays a key role in the diagnosis of the *** w

关键词： Thymic tumor Salivary gland carcinoma Mucoepidermoid carcinoma Postoperative Radiotherapy Case report

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Targeting cancer cell plasticity by HDAC inhibition to reverse EBV-induced dedifferentiation in nasopharyngeal carcinoma

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Signal Transduction and Targeted Therapy 2021年第10期6卷 3045-3061页

作者： Jiajun Xie Zifeng Wang Wenjun Fan Youping Liu Fang Liu Xiangbo Wan Meiling Liu Xuan Wang Deshun Zeng Van Wang Bin He Min Yan Zijian Zhang Mengjuan Zhang Zhijie Hou Chunli Wang Zhijie Kang Wenfeng Fang Li Zhang Eric W-F Lam Xiang Guo Jinsong Yan Yixin Zeng Mingyuan Chen Quentin Liu Sun Yat-sen University Cancer Center State Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer MedicineGuangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and TherapyGuangzhouChina Institute of Cancer Stem Cell Cancer CenterDalian Medical UniversityDalianChina Department of Hematology Liaoning Key Laboratory of Hematopoietic Stem Cell Transplantation and Translational MedicineLiaoning Medical Center for Hematopoietic Stem Cell TransplantationDalian Key Laboratory of HematologyDiamond Bay Institute of HematologyThe Affiliated Second Hospital of Dalian Medical UniversityDalianChina Department of Radiation oncology The Sixth Affiliated Hospital of Sun Yat-sen UniversityGuangzhouChina Sun Yat-sen Institute of Hematology The Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhouChina

Application of differentiation therapy targeting cellular plasticity for the treatment of solid malignancies has been *** carci noma(NPC)is a distinctive cancer with poor differe ntiatio n and high prevalenee of Epstein-Barr virus(EBV)***,we show that the expressi on of EBV latent protein LMP1 in duces dediffere ntiated and stem-like status with high plasticity through the transcriptional inhibition of ***,LMP1 upregulates STAT5A and recruits HDAC 1/2 to the CEBPA locus to reduce its histone *** inhibition restored CEBPA expression,reversing cellular dedifferentiation and stem-like status in mouse xeno graft *** fin dings provide a novel mecha nistic epigenetic-based in sight into virus-induced cellular plasticity and propose a promising concept of differentiation therapy in solid tumor by using HDAC inhibitors to target cellular plasticity.

关键词： LMP1 cancer plasticity

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SETD2 mediates immunotherapy and radiotherapy efficacy via regulating DNA damage responses and genomic stability in lung adenocarcinoma

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Genes & Diseases 2023年第2期10卷 336-339页

作者： Zihang Zeng Yanping Gao Jiali Li Jianguo Zhang Yangyi Li Fajian He Zhengrong Huang Linzhi Han Yan Gong Conghua Xie Department of Radiation and Medical oncology Zhongnan Hospital of Wuhan UniversityWuhanHubei 430071China Department of Biological Repositories Zhongnan Hospital of Wuhan UniversityWuhanHubei 430071China Tumor Precision diagnosis and treatment technology and Translational Medicine Hubei Engineering Research CenterZhongnan Hospital of Wuhan UniversityWuhanHubei 430071China Hubei key laboratory of Tumor Biological Behaviors Zhongnan Hospital of Wuhan UniversityWuhanHubei 430071China Hubei Cancer Clinical Study Center Zhongnan Hospital of Wuhan UniversityWuhanHubei 430071China

SETD2 is the main transferase for the trimethylation of histone H3 at lysine 36 (H3K36me3) in mammals. SETD2 plays important role in repairing DNA double strand breaks and maintaining chromatin integrity.1 In renal carcinoma, SETD2 deficiency caused DNA replication fork instability and DNA damage.2 The absence of SETD2 was also reported to have strong tumor-promoting effects in lung adenocarcinomas (LUAD).3 However, the other roles of SETD2 remain poorly understood in LUAD. In this study, we utilized comprehensive omics-data analysis to determine that SETD2 was associated with DNA damage and immune-related signals in LUAD. SETD2 knockdown induced DNA damage and cGAS activation in LUAD cells, and reduced the number of cells at the G1 phase. Moreover, SETD2 deficiency was conducive to mutation burden, immune cell infiltration, and immunotherapy responses. High SETD2 expression was associated with high radiocurability. These findings suggest that SETD2 may be a promising biomarker of therapeutic responses for LUAD patients, and offer novel insights into immunotherapy and radiotherapy.

关键词： SETD2 damage immunotherapy

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The diagnostic and prognostic values of plasma Epstein-Barr virus DNA for residual cervical lymphadenopathy in nasopharyngeal carcinoma patients:a retrospective study

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Cancer Communications 2019年第1期39卷 135-147页

作者： Sai-Lan Liu Xue-Song Sun Xiao-Yun Li Lin-Quan Tang Qiu-Yan Chen Huan-Xin Lin Yu-Jing Liang Jin-Jie Yan Chao Lin Shan-Shan Guo Li-Ting Liu Yang Li Hao-Jun Xie Qing-Nan Tang Hu Liang Ling Guo Hai-Qiang Mai State key laboratory of oncology in South China Collaborative Innovation Center for Cancer MedicineGuangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and TherapySun Yat-sen University Cancer CenterGuangzhou 510060GuangdongP.R.China Department of Nasopharyngeal Carcinoma Sun Yat-sen University Cancer CenterGuangzhou 510060Guang-dongP.R.China Department of Radiation oncology Sun Yat-sen University Cancer CenterGuangzhou 510060GuangdongP.R.China

Background:Currently,the diagnosis and treatment of nasopharyngeal carcinoma(NPC)patients with residual cervical lymphadenopathy following radical radiotherapy with or without chemotherapy are *** investigated the prognosis of NPC patients with residual cervical lymphadenopathy and assessed the diagnostic and prognostic values of Epstein-Barr virus(EBV)DNA in these ***:This study included 82 NPC patients who were diagnosed with suspected residual cervical lymphadenopathy following completion of antitumor *** plasma EBV DNA levels were measured using quantitative polymerase chain reaction(qPCR)before the initiation of treatment and before neck *** needle aspiration cytology(FNAC)was performed in 21 *** patients had undergone neck dissection and postoperative pathological examination to identify the nature of residual cervical *** overall survival(OS),progression-free survival(PFS),distant metastasis-free survival(DMFS),and locoregional relapse-free survival(LRRFS)were calculated using the Kaplan-Meier method and compared using the log-rank *** Cox proportional hazards model was used to calculate hazard ratios(HRs)with 95%confidence intervals(CIs).Multivariable analysis was used to estimate the effect of potential prognostic factors on ***:Following a median follow-up of 52.6 months,compared with patients with negative postoperative pathological findings for residual cervical lymphadenopathy,the patients with positive findings had a significantly lower 3-year PFS rate(49.9%vs.83.3%,P=0.008).Among NPC patients with residual cervical lymphadenopathy,the patients with preoperative plasma EBV DNA>0 copy/mL had a lower 3-year PFS rate than did those with no detectable EBV DNA(43.7%vs.61.1%,P=0.031).In addition,combining FNAC with preoperative EBV DNA detection improved the diagnostic *** analysis demonstrated that residual cervical lymphadenopathy with positive po

关键词： Nasopharyngeal carcinoma Residual cervical lymphadenopathy Prognosis Epstein-Barr virus Fine needle aspiration cytology Survival

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A Novel Diagnostic and Therapeutic Strategy for Cancer Patients by Integrating Chinese Medicine Syndrome Differentiation and Precision Medicine

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Chinese Journal of Integrative Medicine 2022年第10期28卷 867-871页

作者： YU Shu-xian LIANG Zi-mao WU Qi-biao SHOU Lan HUANG Xing-xing ZHU Qian-ru XIE Han MEI Ru-yi ZHANG Ruo-nan ZHAI Xiang-yang XIE Tian SUI Xin-bing School of Pharmacy and Department of Medical oncology the Afﬁliated Hospital of Hangzhou Normal UniversityCollege of MedicineHangzhou Normal UniversityHangzhou(311121)China key laboratory of Elemene Class Anti-cancer Chinese Medicines Engineering Laboratory of Development and Application of Traditional Chinese MedicinesCollaborative Innovation Center of Traditional Chinese Medicines of Zhejiang ProvinceHangzhou Normal UniversityHangzhou(311121)China State key laboratory of Quality Research in Chinese Medicines Faculty of Chinese MedicineMacao University of Science and TechnologyMacaoChina

Applying Chinese medicine(CM) is an important strategy for malignant tumor treatment in China. One of the significant characteristics of CM is to treat diseases based on syndrome differentiation. For Western medicine, it is of important clinical significance to formulate guidelines for the diagnosis and treatment of cancer patients based on the characteristics of disease differentiation. In Chinese clinical practice, the combination of disease differentiation and syndrome differentiation is an important feature for cancer treatment in the past. Currently, molecular profiling and genomic analysis-based precision medicine optimizes the anticancer drug design and holds the greatest success in treating cancer patients. Therefore, we want to know which populations of cancer patients can benefit more from CM treatment if the theory of precision medicine is applied to CM clinical practice. So, we developed a novel diagnostic and therapeutic strategy "disease-syndrome differentiation-genomic profilingprescriptions" for cancer patients by CM syndrome differentiation and precision medicine. As a result, this strategy has greatly enhanced the anti-tumor efficacy of CM and improved clinical outcomes for cancer patients with some gene mutations. Our idea will hopefully establish a novel approach for the inheritance and innovation of CM.

关键词： Chinese medicine Western medicine syndrome differentiation precision medicine cancer treatment

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