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Deletion of the RNA-editing enzyme ADAR1A: new strategy to potentiate responses to PD-1 immune checkpoint blockade

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Signal Transduction and Targeted Therapy 2019年第1期4卷 590-591页

作者： manni wang Xiawei Wei Laboratory of Aging Research and Cancer Drug Target State Key Laboratory of Biotherapy and Cancer CenterNational Clinical Research Center for GeriatricsWest China HospitalSichuan UniversityNo.17Block 3Southern Renmin RoadChengdu610041SichuanPeople’s Republic of China

In a recent study in Nature,Ishizuka et al.1 proposed a new strategy to restore sensitivity to immune checkpoint blockades(ICBs)through the loss of RNA-editing enzyme ADAR1(adenine deaminase acting on RNA 1).This find... 详细信息

关键词： ADAR1 al. attractive

Molecular mechanisms and clinical management of cancer bone metastasis

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Bone Research 2020年第3期8卷 266-285页

作者： manni wang Fan Xia Yuquan Wei Xiawei Wei Laboratory of Aging Research and Cancer Drug Targets State Key Laboratory of Biotherapy and Cancer CenterNational Clinical Research Center for GeriatricsWest China HospitalSichuan UniversityNo.17Block 3Southern Renmin RoadChengdu 610041 SichuanP.R.China Department of Neurosurgery West China HospitalSichuan UniversityChengdu 610041 SichuanP.R.China

As one of the most common metastatic sites of malignancies,bone has a unique microenvironment that allows metastatic tumor cells to grow and *** fenestrated capillaries in the bone,bone matrix,and bone cells,including osteoblasts and osteoclasts,together maintain the homeostasis of the bone *** contrast,tumor-derived factors act on bone components,leading to subsequent bone resorption or excessive bone *** various pathways involved also provide multiple targets for therapeutic strategies against bone *** this review,we summarize the current understanding of the mechanism of bone *** on the general process of bone metastases,we specifically highlight the complex crosstalk between tumor cells and the bone microenvironment and the current management of cancer bone metastases.

关键词： metastasis homeostasis cancer

Constrained surfaces: promising therapeutic targets for COVID-19 determined by systematically mutational analysis

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Signal Transduction and Targeted Therapy 2021年第2期6卷 204-205页

作者： manni wang Tianxia Lan Wei wang Laboratory of Aging Research and Cancer Drug Targets State Key Laboratory of Biotherapy and Cancer CenterNational Clinical Research Center for GeriatricsWest China HospitalSichuan UniversityNo.17Block 3Renmin Road SouthChengduSichuan 610041P.R.China

A recent study published in Cell by Tyler *** et al. presented a quantitative deep mutational scanning platform that allowed for the characterization of potential amino acid(AA)mutations to the SARS-CoV-2 receptor binding domain(RBD).The mutationphenotype maps provided in this work determined the influence of RBD expression and binding affinity to human cell-surface protein angiotensin-converting enzyme 2(ACE2)induced by fully random substitution for each AA of *** work identified pivotal positions for virus binding and entry into cells,facilitating the development of countermeasures for COVID-19,such as vaccines.

关键词： al. therapeutic allowed

DNA-PK inhibition by M3814 enhances chemosensitivity in non-small cell lung cancer

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Acta Pharmaceutica Sinica B 2021年第12期11卷 3935-3949页

作者： manni wang Siyuan Chen Yuquan Wei Xiawei Wei Laboratory of Aging Research and Cancer Drug Target State Key Laboratory of Biotherapy and Cancer CenterNational Clinical Research Center for GeriatricsWest China HospitalSichuan UniversityChengdu 610000China

A significant proportion of non-small cell lung cancer(NSCLC) patients experience accumulating chemotherapy-related adverse events,motivating the design of chemosensitizating *** main cytotoxic damage induced by chemotherapeutic agents is DNA double-strand breaks(DSB).It is thus conceivable that DNA-dependent protein kinase(DNA-PK) inhibitors which attenuate DNA repair would enhance the anti-tumor effect of *** present study aims to systematically evaluate the efficacy and safety of a novel DNA-PK inhibitor M3814 in synergy with chemotherapies on *** identified increased expression of DNA-PK in human NSCLC tissues which was associated with poor prognosis.M3814 potentiated the anti-tumor effect of paclitaxel and etoposide in A549,H460 and H1703 NSCLC cell *** the four combinations based on two NSCLC xenograft models and two chemotherapy,we also observed tumor regression at tolerated doses in ***,we identified a P53-dependent accelerated senescence response by M3814 following treatment with paclitaxel/*** present study provides a theoretical basis for the use of M3814 in combination with paclitaxel and etoposide in clinical practice,with hope to aid the optimization of NSCLC treatment.

关键词： M3814 Paclitaxel Etoposide DNA-dependent protein kinase Non-small cell lung cancer DNA repair Cell senescence Chemosensitization

Clonal replacement of novel T cells: a new phenomenon in the tumor microenvironment following PD-1 blockade

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Signal Transduction and Targeted Therapy 2019年第1期4卷 243-244页

作者： Xue Li manni wang Rong Xiang Department of Biotherapy State Key Laboratory of Biotherapy and Cancer CenterWest China HospitalSichuan UniversityNo.17Block 3Southern Renmin Road610041 ChengduSichuanChina Department of Immunology School of MedicineNankai UniversityTianjinChina

In a recent study published in Nature Medicine,Yost et al.1 described the clonal replacement of tumor-specific T cells after treatment with PD-1 *** finding reveals the intrinsic ability of the tumor microenvironment to attract new T cells,which has crucial applications for the design of immune checkpoint blockade(ICB)therapies(Fig.1).Over the past few decades,ICB therapies have been successful in some patients with different types of cancer by blocking inhibitory checkpoint receptors on T cells,and thus restoring T cell-mediated immune responses as well as recruiting more T cells into the tumor environment.

关键词： al. tumor Medicine

Nanoparticles targeting tumor-associated macrophages:A novel anti-tumor therapy

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Nano Research 2022年第3期15卷 2177-2195页

作者： Siyuan Chen Furong Qin manni wang Yuquan Wei Zhiyong Qian Xiawei Wei Laboratory of Aging Research and Cancer Drug Target State Key Laboratory of BiotherapyNational Clinical Research Center for GeriatricsWest China HospitalSichuan UniversityChengdu 610041China

The immunosuppressive tumor microenvironment(TME)is crucial in the occurrence of tumorigenesis,metastasis,and drug *** all stromal cells,tumor-associated macrophages(TAMs)are recognized as vital components causing the TME to be favorable for cancer cells and are also main targets in cancer *** date,nanoparticle(NP)-based drug delivery systems,as new technology platforms,have exhibited considerable advantages,such as targeted drug delivery at tumor sites,enhanced drug transport efficiency,and controllable drug release profiles,which provide new approaches for cancer *** TAM-targeting nanoparticles,various therapeutic strategies have been developed by varying their design,namely,by blocking TAM recruitment,promoting TAM transformation,and directly diminishing existing *** the current review,we provide a brief overview of the role of TAMs in the tumor microenvironment and their functions and highlight strategies for TAM ***,the applications of nanoparticles in targeting TAMs to improve cancer therapeutic efficiency are summarized.

关键词： tumors immunotherapy tumor-associated macrophages nanoparticles

JMJD family proteins in cancer and inflammation

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Signal Transduction and Targeted Therapy 2022年第10期7卷 3665-3686页

作者： wang manni Xue Jianxin Hong Weiqi Chen Siyuan Shi Huashan Department of Biotherapy Cancer CenterWest China HospitalSichuan UniversityNo.17Block 3Southern Renmin Road610041 ChengduSichuanPR China Department of Thoracic Oncology Cancer Center and State Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengduChina Laboratory of Aging Research and Nanotoxicology State Key Laboratory of BiotherapyNational Clinical Research Center for GeriatricsWest China HospitalSichuan University610041 ChengduSichuanPR China

The occurrence of cancer entails a series of genetic mutations that favor uncontrollable tumor *** is believed that various factors collectively contribute to cancer,and there is no one single explanation for *** changes such as the dysregulation of enzymes modifying DNA or histones are actively involved in oncogenesis and inflammatory *** methylation of lysine residues on histone proteins represents a class of post-translational *** human Jumonji C domain-containing(JMJD)protein family consists of more than 30 *** JMJD proteins have long been identified with histone lysine demethylases(KDM)and histone arginine demethylases activities and thus could function as epigenetic modulators in physiological processes and ***,growing evidence has demonstrated the aberrant expression of JMJD proteins in cancer and inflammatory diseases,which might serve as an underlying mechanism for the initiation and progression of such ***,we discuss the role of key JMJD proteins in cancer and inflammation,including the intensively studied histone lysine demethylases,as well as the understudied group of JMJD *** particular,we focused on epigenetic changes induced by each JMJD member and summarized recent research progress evaluating their therapeutic potential for the treatment of cancer and inflammatory diseases.

关键词： inflammation JMJD collective

Role of tumor gene mutations in treatment response to immune checkpoint blockades

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Precision Clinical Medicine 2019年第2期2卷 100-109页

作者： manni wang Liu Yu Xiawei Wei Yuquan Wei Laboratory of Aging Research and Nanotoxicology State Key Laboratory of BiotherapyNational Clinical Research Center for GeriatricsWest China HospitalSichuan UniversityNo.17Block 3Southern Renmin RoadChengdu 610041PR China

Early studies shed light on the immune suppression of immune checkpoint molecules in the cancer microenvironment,with later studies applying immune checkpoint blockade(ICB)in treatment of various *** the encouraging efficacy of ICBs in a substantial subset of cancer patients,the treatment response *** mutations of both tumor cells and immune cells in the tumor microenvironment have recently been identified as potential predictors of the ICB *** developments in gene expression profiling of tumors have allowed identification of a panel of mutated genes that may affect tumor cell response to ICB *** this review,we discuss the association of the ICB response with gene expression and mutation profiles in tumor cells,which it is hoped will help to optimize the clinical application of ICBs in cancer patients.

关键词： gene mutation immune checkpoint blockade tumor

Targeting epigenetic regulators for cancer therapy: mechanisms and advances in clinical trials

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Signal Transduction and Targeted Therapy 2019年第1期4卷 63-101页

作者： Yuan Cheng Cai He manni wang Xuelei Ma Fei Mo Shengyong Yang Junhong Han Xiawei Wei Laboratory of Aging Research and Cancer Drug Target State Key Laboratory of Biotherapy and Cancer CenterNational Clinical Research Center for GeriatricsWest China HospitalSichuan UniversityChengduChina

Epigenetic alternations concern heritable yet reversible changes in histone or DNA modifications that regulate gene activity beyond the underlying *** dysregulation is often linked to human disease,notably *** the development of various drugs targeting epigenetic regulators,epigenetic-targeted therapy has been applied in the treatment of hematological malignancies and has exhibited viable therapeutic potential for solid tumors in preclinical and clinical *** this review,we summarize the aberrant functions of enzymes in DNA methylation,histone acetylation and histone methylation during tumor progression and highlight the development of inhibitors of or drugs targeted at epigenetic enzymes.

关键词： epigenetic clinical drugs