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| 1 | Annual progress of clinical research on targeted therapy for nonsmall cell lung cancer in 2022显示文摘With the rapid development of lung cancer molecular detection and precisiontherapy, targeted therapy has covered the entire process of diagnosis andtreatment of nonsmall cell lung cancer patients. Overall mortality from lungcancer has decreased significantly over the past 20 years, especially since theintroduction of targeted drugs in 2013. In 2022, targeted therapy for lungcancer has developed rapidly. The optimization of treatment modes and theexploration of new target drugs such as antibody‐drug conjugates will broadenthe selection range of nonsmall cell lung cancer patients with positive drivergenes. This article reviews the latest advances in targeted therapy for drivergene‐positive lung cancer in 2022. | Yan Huang Li Zhang | 2023 | Cancer Innovation2023，2，1： | 1 |
| 2 | Treatment‐related adverse events of antibody‐drug conjugates in clinical trials:A systematic review and meta‐analysis显示文摘Background:The wide use of antibody‐drug conjugates(ADCs)is transforming the cancer‐treatment landscape.Understanding the treatment‐related adverse events(AEs)of ADCs is crucial for their clinical application.We conducted a meta‐analysis to analyze the profile and incidence of AEs related to ADC use in the treatment of solid tumors and hematological malignancies.Methods:We searched the PubMed,Embase,and Cochrane Library databases for articles published from January 2001 to October 2022.The overall profile and incidence of all‐grade and grade≥3 treatment‐related AEs were the primary outcomes of the analysis.Results:A total of 138 trials involving 15,473 patients were included in this study.The overall incidence of any‐grade treatment‐related AEs was 100.0%(95%confidence interval[CI]:99.9%–100.0%;I2=89%)and the incidence of grade≥3 treatment‐related AEs was 6.2%(95%CI:3.0%–12.4%;I2=99%).Conclusions:This study provides a comprehensive overview of AEs related to ADCs used for cancer treatment.ADC use resulted in a high incidence of any‐grade AEs but a low incidence of grade≥3 AEs.The AE profiles and incidence differed according to cancer type,ADC type,and ADC components. | Jinming Li Guoshuang Shen Zhen Liu Yaobang Liu Miaozhou Wang Fuxing Zhao Dengfeng Ren Qiqi Xie Zitao Li Zhilin Liu Yi Zhao Fei Ma Xinlan Liu Zhengbo Xu Jiuda Zhao | 2023 | Cancer Innovation2023，2，5： | 1 |
| 3 | ATF4/TXNIP/REDD1/mTOR signaling mediates the antitumor activities of liver X receptor in pancreatic cancers显示文摘Background:Limited by difficulties in early detection and availabilities of effective treatments,pancreatic cancer is a highly malignant disease with poor prognosis.Nuclear receptors are a family of ligand‐dependent transcription factors that are highly druggable therapeutic targets playing critical roles in human physiological and pathological development,including cancer.In this study,we explored the therapeutic potential as well as the molecular mechanisms of liver X receptor(LXR)agonist GW3965 in pancreatic cancer.Methods:Soft‐agar colony formation assay,xenograft tumors,Oligonucleotide microarray,Reverse transcription real‐time polymerase chain reaction,Western immunoblotting and Immunohistochemistry were used in this study.Results:We demonstrated pleotropic in vitro activities of GW3965 in pancreatic cell lines MIA PaCa‐2 and BXPC3 including reduction of cell viability,inhibition of cell proliferation,stimulation of cell death,and suppression of colony formation,which translated to significant inhibition of xenograft tumor growth in vitro.By mapping the gene expression profiles,we identified the up‐regulations of 188 and the down‐regulations of 92 genes common to both cell lines following GW3965 treatment.Genes responsive to GW3965 represent a variety of biological pathways vital for multiple cellular functions.Specifically,we identified that the activating transcription factor 4/thioredoxin‐interacting protein/regulated in development and DNA damage responses 1/mechanistic target of rapamycin(ATF4/TXNIP/REDD1/mTOR)signaling critically controls GW3965‐mediated regulation of cell proliferation/death.The significance of the ATF4/TXNIP/REDD1/mTOR pathway was further supported by associated expressions in xenograft tumors as well as human pancreatic cancer samples.Conclusions:This study provides the pre‐clinical evidence that LXR agonist is a promising therapy for pancreatic cancer. | Zhikang Chen Xiaobo Lai Hui Ding Aijun Zhang Yufei Sun Jianhua Ling Paul J.Chiao Zihua Chen Xuefeng Xia | 2022 | Cancer Innovation2022，1，1： | 1 |
| 4 | Crosstalk between ferroptosis and stress—Implications in cancer therapeutic responses显示文摘Ferroptosis is a newly discovered form of cell death that is characterized by the accumulation of iron‐dependent lipid peroxidation.Research on ferroptosis has seen exponential growth over the past few years.Tumor cells are strongly dependent on iron for their growth,which makes them develop mechanisms to increase iron uptake and inhibit iron output,thereby completing iron accumulation.Ferroptosis can be induced or inhibited by various stresses through multiple mechanisms,making it stands at the crossroads of stresses related cancer cell fate determination.In this review,we give a brief summary of ferroptosis hallmarks and provide a systematic analysis of the current molecular mechanisms and regulatory networks of diverse stress conditions on ferroptosis.We also discuss the relationships between ferroptosis and cancer therapy responses to further understand potential targets and therapeutic strategies for cancer treatment. | Cheng Zhang Jiao‐jiao Yu Chen Yang Shuang Shang Xiao‐xi Lv Bing Cui Fang Hua | 2022 | Cancer Innovation2022，1，1： | 1 |
| 5 | Resveratrol activation of SIRT1/MFN2 can improve mitochondria function,alleviating doxorubicin-induced myocardial injury显示文摘Background Doxorubicin is a widely used cytotoxic chemotherapy agent for treating different malignancies.However,its use is associated with dose-dependent cardiotoxicity,causing irreversible myocardial damage and significantly reducing the patient's quality of life and survival.In this study,an animal model of doxorubicin-induced cardiomyopathy was used to investigate the pathogenesis of doxorubicin-induced myocardial injury.This study also investigated a possible treatment strategy for alleviating myocardial injury through resveratrol therapy in vitro.Methods Adult male C57BL/6J mice were randomly divided into a control group and a doxorubicin group.Body weight,echocardiography,surface electrocardiogram,and myocardial histomorphology were measured.The mechanisms of doxorubicin cardiotoxicity in H9c2 cell lines were explored by comparing three groups(phosphate-buffered saline,doxorubicin,and doxorubicin with resveratrol).Results Compared to the control group,the doxorubicin group showed a lower body weight and higher systolic arterial pressure,associated with reduced left ventricular ejection fraction and left ventricular fractional shortening,prolonged PR interval,and QT interval.These abnormalities were associated with vacuolation and increased disorder in the mitochondria of cardiomyocytes,increased protein expression levels of α-smooth muscle actin and caspase 3,and reduced protein expression levels of Mitofusin2(MFN2)and Sirtuin1(SIRT1).Compared to the doxorubicin group,doxorubicin+resveratrol treatment reduced caspase 3 and manganese superoxide dismutase,and increased MFN2 and SIRT1 expression levels.Conclusion Doxorubicin toxicity leads to abnormal mitochondrial morphology and dysfunction in cardiomyocytes and induces apoptosis by interfering with mitochondrial fusion.Resveratrol ameliorates doxorubicin-induced cardiotoxicity by activating SIRT1/MFN2 to improve mitochondria function. | Qingling Zhang Yunpeng Zhang Bingxin Xie Daiqi Liu Yueying Wang Zandong Zhou Yue Zhang Emma King Gary Tse Tong Liu | 2023 | Cancer Innovation2023，2，4： | 1 |
| 6 | The inaugurationof Cancer Innovation Leading New Frontiers in Oncology,Building Human Health Community显示文摘Cancer is a challenging disease to both understand and treat,and was responsible for 17.8%of total deaths worldwide in 2020,coming closer to the 20.6%of deaths associated with cardiovascular disease.Despite global oncology spending of 167 billion US dollars in 2020,the prognosis of most cancers,especially advanced‐stage diseases,remains poor because of therapy resistance.With much emphasis and many resources placed on oncological research,progress in precancer screening,anticancer treatments,and supportive care all contribute to better survival rates and quality of life for cancer patients. | Fei Ma | 2022 | Cancer Innovation2022，1，1： | 0 |
| 7 | Expert consensus on the clinical application of antibody‐drug conjugates in the treatment of malignant tumors(2021 edition)显示文摘Antibody‐drug conjugates(ADCs)are targeted biological agents composed of a cytotoxic drug linked to a monoclonal antibody through a linker.The monoclonal antibody targets tumor cells and transports small‐molecule cytotoxic drugs for specific delivery and minimal off‐target side effects.It is necessary for clinicians to understand the molecular characteristics and mechanisms of ADCs.Patients'survival mainly depends on the appropriate dose and course of treatment and also on proper management of adverse reactions.This consensus provides a systematic review of commercially available ADCs and further discusses the clinical application and management of ADCs. | Professional Committee on Clinical Research of Oncology Drugs,Chinese Anti‐Cancer Association Expert Committee for Monitoring the Clinical Application of Antitumor Drugs Breast Cancer Expert Committee of National Cancer Quality Control Center| Cancer Chemotherapy Quality Control Expert Committee of Beijing Cancer Treatment Quality Control and Improvement Center Fei Ma Binghe Xu | 2022 | Cancer Innovation2022，1，1： | 0 |
| 8 | Expert consensus on the clinical application of PI3K/AKT/mTOR inhibitors in the treatment of advanced breast cancer显示文摘Phosphoinositide 3‐kinase(PI3K)/protein kinase B(PKB or AKT)/mammalian target of rapamycin(mTOR)signaling pathway(PAM pathway)plays an important role in the development of breast cancer and are closely associated with the resistance to endocrine therapy in advanced breast cancer.Therefore,anticancer treatment targeting key molecules in this signaling pathway has become a research hotspot in recent years.Randomized clinical trials have demonstrated that PI3K/AKT/mTOR inhibitors bring significant clinical benefit to patients with advanced breast cancer,especially to those with hormone receptor(HR)‐positive,human epidermal growth factor receptor(HER)2‐negative advanced breast cancer.Alpelisib,a PI3K inhibitor,and everolimus,an mTOR inhibitor,have been approved by FDA.Based on their high efficacy and relatively good safety profile,an expanded indication of everolimus in breast cancer has been approved by National Medical Products Administration(NMPA).Alpelisib is expected to be approved in China in the near future.The members of the consensus expert panel reached this consensus to comprehensively define the role of PI3K/AKT/mTOR signaling pathway in breast cancer,efficacy and clinical applications of PI3K/AKT/mTOR inhibitors,management of adverse reactions,and PIK3CA mutation detection,to promote the understanding of PI3K/AKT/mTOR inhibitors for Chinese oncologists,improve clinical decision‐making,and prolong the survival of target patient population. | The Society of Clinical Research of Oncology Medications of China Anticancer Association Breast Cancer Expert Committee of National Cancer Quality Control Center Boao Cancer Innovation Institute Fei Ma Binghe Xu | 2022 | Cancer Innovation2022，1，1： | 0 |
| 9 | Genetic variants in XPD gene and glioma susceptibility in Chinese children:A multicenter case–control study显示文摘Background:Glioma is one of the central nervous system(CNS)tumors in children,accounting for 80%of malignant brain tumors.Nucleotide excision repair(NER)is a vital pathway during DNA damage repair progression.Xeroderma pigmentosum group D(XPD)or excision repair cross‐complementing group 2(ERCC2)is a critical factor in the NER pathway,playing an indispensable role in the DNA repair process.Therefore,the genetic variants in XPD may be associated with carcinogenesis induced by defects in DNA repair.Methods:We are the first to conduct a multi‐center case‐control study to investigate the correlation between XPD gene polymorphisms and pediatric glioma risk.We chose three single nucleotide polymorphisms and genotyped them using the TaqMan assay.Results:Although there is no significant association of these genetic variations with glioma susceptibility,the stratified analysis revealed that in the subtype of astrocytic tumors,the rs13181 TG/GG genotype enhanced glioma risk than the TT genotype,and carriers with two to three genotypes also elevated the tumor risk than 0‐1 genotypes.Conclusion:In conclusion,our findings provided an insight into the impact of XPD genetic variants on glioma risk. | Yong‐Ping Chen Yuxiang Liao Li Yuan Xiao‐Kai Huang Ji‐Chen Ruan Hui‐Ran Lin Lei Miao Zhen‐Jian Zhuo | 2022 | Cancer Innovation2022，1，1： | 0 |
| 10 | Application of informatics in cancer research and clinical practice:Opportunities and challenges显示文摘Cancer informatics has significantly progressed in the big data era.We summarize the application of informatics approaches to the cancer domain from both the informatics perspective(e.g.,data management and data science)and the clinical perspective(e.g.,cancer screening,risk assessment,diagnosis,treatment,and prognosis).We discuss various informatics methods and tools that are widely applied in cancer research and practices,such as cancer databases,data standards,terminologies,high‐throughput omics data mining,machine‐learning algorithms,artificial intelligence imaging,and intelligent radiation.We also address the informatics challenges within the cancer field that pursue better treatment decisions and patient outcomes,and focus on how informatics can provide opportunities for cancer research and practices.Finally,we conclude that the interdisciplinary nature of cancer informatics and collaborations are major drivers for future research and applications in clinical practices.It is hoped that this review is instrumental for cancer researchers and clinicians with its informatics‐specific insights. | Na Hong Gang Sun Xiuran Zuo Meng Chen Li Liu Jiani Wang Xiaobin Feng Wenzhao Shi Mengchun Gong Pengcheng Ma | 2022 | Cancer Innovation2022，1，1： | 0 |
| 11 | Identification of novel somatic fusions of ERG‐VEGFA,TMPRSS2‐ERG,and VEGFA‐TMPRSS2 in prostate cancer treated with anlotinib and androgen deprivation therapy:A case report显示文摘The TMPRSS2‐ERG fusion gene has frequently been found in prostate cancer and is associated with malignancy.Identifying novel fusions will help to stratify patients and establish patient‐tailored therapies.A 78‐year‐old man presented to our hospital with severe symptoms of urinary urgency and frequency for 2 years,as well as severe bone pain for 1 year.He was diagnosed with metastatic prostate cancer with a Gleason score of 5+5.Three gene fusions,ERG_VEGFA,TMPRSS2_ERG,and VEGFA_TMPRSS2,were identified in the patient's prostate cancer tissue.Notably,administration of the tyrosine kinase inhibitor,anlotinib,in combination with a gonadotropinreleasing hormone agonist(GnRHa)and abiraterone,reduced the patient's bone pain and also stabilized his prostate cancer for more than 2 years.This is the first report of somatic fusions among the VEGFA,ERG,and TMPRSS2 genes in cancer tissues from a patient with prostate cancer who responded well to antiangiogenic treatment combined with a GnRHa and abiraterone. | Qiuli Liu Shuo Wang Ze Wang Peng Tang Dianzheng Zhang Weihua Lan Jun Jiang | 2022 | Cancer Innovation2022，1，1： | 0 |
| 12 | Advances in the role of circulating tumor cell heterogeneity in metastatic small cell lung cancer显示文摘Small cell lung cancer(SCLC),a highly aggressive malignancy,is rapidly at an extensive stage once diagnosed and is one of the leading causes of death from malignancy.In the past decade,the treatment of SCLC has largely remained unchanged,and chemotherapy remains the cornerstone of SCLC treatment.The therapeutic value of adding immune checkpoint inhibitors to chemotherapy for SCLC is low,and only a few SCLC patients have shown a response to immune checkpoint inhibitors.Circulating tumor cells(CTCs)are tumor cells shed from solid tumor masses into the peripheral circulation and are key to tumor metastasis.Single-cell sequencing has revealed that the genetic profiles of individual CTCs are highly heterogeneous and contribute to the poor outcome and prognosis of SCLC patients.Theoretically,phenotypic analysis of CTCs may be able to predict the diagnostic significance of new potential targets for metastatic tumors.In this paper,we will discuss in depth the heterogeneity of CTCs in SCLC and the value of CTCs for the diagnosis and prognosis of SCLC and as relevant tumor markers in metastatic SCLC. | Qunxia Wang Li-Ming Tan | 2024 | Cancer Innovation2024，3，2： | 0 |
| 13 | Multifaceted roles and functions of SOX30 in human cancer显示文摘SRY-box transcription factor 30(SOX30)participates in tumor cell apoptosis in lung cancer.The occurrence of somatic SOX30 mutations,the expression signature of SOX30 in normal and cancer tissues,the correlation of SOX30 with immune cells and immune-related genes,and the clinical significance of SOX30 in various cancers have stimulated interest in SOX30 as a potential cancer biomarker.SOX30 influences drug sensitivity and tumor immunity in specific cancer types.In this review,we have comprehensively summarized the latest research on the role of SOX30 in cancer by combining bioinformatics evidence and a literature review.We summarize recent research on SOX30 in cancer regarding somatic mutations,trials,transcriptome analysis,clinical information,and SOX30-mediated regulation of malignant phenotypes.Additionally,we report on the diagnostic value of SOX30 mRNA expression levels across different cancer types.This review on the role of SOX30 in cancer progression may provide insights into possible research directions for SOX30 in cancer and a theoretical basis for guiding future studies. | Na Sun Cheng Wang Pingping Gao Rui Wang Yi Zhang Xiaowei Qi | 2024 | Cancer Innovation2024，3，2： | 0 |
| 14 | Cardiovascular disease burden in patients with urological cancers:The new discipline of uro-cardio-oncology显示文摘Cancer remains a major cause of mortality worldwide,and urological cancers are the most common cancers among men.Several therapeutic agents have been used to treat urological cancer,leading to improved survival for patients.However,this has been accompanied by an increase in the frequency of survivors with cardiovascular complications caused by anticancer medications.Here,we propose the novel discipline of uro-cardio-oncology,an evolving subspecialty focused on the complex interactions between cardiovascular disease and urological cancer.In this comprehensive review,we discuss the various cardiovascular toxicities induced by different classes of antineoplastic agents used to treat urological cancers,including androgen deprivation therapy,vascular endothelial growth factor receptor tyrosine kinase inhibitors,immune checkpoint inhibitors,and chemotherapeutics.In addition,we discuss possible mechanisms underlying the cardiovascular toxicity associated with anticancer therapy and outline strategies for the surveillance,diagnosis,and effective management of cardiovascular complications.Finally,we provide an analysis of future perspectives in this emerging specialty,identifying areas in need of further research. | Yi Zheng Ying Liu Ziliang Chen Yunpeng Zhang Zuo Qi Ning Wu Zhiqiang Zhao Gary Tse Yong Wang Hailong Hu Yuanjie Niu Tong Liu | 2024 | Cancer Innovation2024，3，2： | 0 |
| 15 | Cancer treatment with biosimilar drugs:A review显示文摘Biosimilars are biological drugs created from living organisms or that contain living components.They share an identical amino-acid sequence and immunogenicity.These drugs are considered to be cost-effective and are utilized in the treatment of cancer and other endocrine disorders.The primary aim of biosimilars is to predict biosimilarity,efficacy,and treatment costs;they are approved by the Food and Drug Administration(FDA)and have no clinical implications.They involve analytical studies to understand the similarities and dissimilarities.A biosimilar manufacturer sets up FDA-approved reference products to evaluate biosimilarity.The contribution of next-generation sequencing is evolving to study the organ tumor and its progression with its impactful therapeutic approach on cancer patients to showcase and target rare mutations.The study shall help to understand the future perspectives of biosimilars for use in gastro-entero-logic diseases,colorectal cancer,and thyroid cancer.They also help target specific organs with essential mutational categories and drug prototypes in clinical practices with blood and liquid biopsy,cell treatment,gene therapy,recombinant therapeutic proteins,and personalized medications.Biosimilar derivatives such as monoclonal antibodies like trastuzumab and rituximab are common drugs used in cancer therapy.Escherichia coli produces more than six antibodies or antibody-derived proteins to treat cancer such as filgrastim,epoetin alfa,and so on. | Shilpa Malakar Emmanuel Nuah Gontor Moses YDugbaye Kamal Shah Sakshi Sinha Priya Sutaoney Nagendra Singh Chauhan | 2024 | Cancer Innovation2024，3，2： | 0 |
| 16 | Comprehensive treatment of von Hippel-Lindau disease:A case report显示文摘von Hippel-Lindau(VHL)disease is a rare autosomal dominant multiorgan disease characterized by several benign and malignant tumors rich in vascular,as well as cysts in other organs.A great clinical treatment strategy is significantly warranted for good prognosis of patients with VHL disease.Herein,we reported a case of a 45-year-old woman diagnosed with VHL disease with spinal hemangioblastoma(HB)and clear cell renal cell carcinoma(ccRCC).Four years after the resection of the right kidney,a recurrent RCC in the right kidney and a malignant lesion in the left kidney were observed.This patient was started on sorafenib(800 mg,daily)and tislelizumab(200 mg per 3 weeks).After 6 months of treatment,the size of renal cell carcinoma was dramatically reduced and renal function improved.More importantly,she achieved partial response during the whole treatment.Microscopically,intramedullary masses resection was done and the HB in T4-5 thoracic spinal was removed.Neurologic symptoms such as numbness and pain were remarkably alleviated.Additionally,tislelizumab-induced elevation in liver transaminase levels and hypothyroidism were revered by hepatoprotector and levothyroxine,respectively.In short,comprehensive treatment strategies may benefit patients with VHL disease,especially with HB and ccRCC. | Xuesong Li Zheng Mo Zhuo Yu | 2024 | Cancer Innovation2024，3，2： | 0 |
| 17 | ^(18)F-FDG PET/CT findings of paratesticular alveolar rhabdomyosarcoma显示文摘Rhabdomyosarcoma(RMS)originates from primitive mesenchymal cells and is the most common soft tissue tumor in childhood.^(18)F-fluoro-deoxyglucose(^(18)F-FDG)positron emission tomography(PET)/computed tomography(CT)has been reported to be valuable in RMS staging and risk stratification.Paratesticular RMS is a relatively uncommon form of RMS,most of which are of the embryonal histologic type.Paratesticular alveolar RMS is associated with aggressive behavior,high metastatic potential,and poor outcomes.To the best of our knowledge,^(18)F-FDG PET/CT imaging findings of paratesticular alveolar RMS have never been described.Here,we report on a 16-year-old boy's rare paratesticular alveolar RMS with multiple metastases and its findings on^(18)F-FDG PET/CT.This case also demonstrates the potential value of^(18)F-FDG PET/CT in RMS staging and treatment decisions,and may aid in the differential diagnosis. | Xueqi Chen Jiayin Shou Shanshi Li Yan Fan Jianhua Zhang | 2024 | Cancer Innovation2024，3，2： | 0 |
| 18 | ALKBH5 gene polymorphisms and risk of neuroblastoma in Chinese children from Jiangsu Province显示文摘Background:Neuroblastoma is one of the most common extracranial malignant solid tumors in children.AlkB homolog 5(ALKBH5)is an RNA N6-methyladenosine(m6A)demethylase that plays a critical role in tumorigenesis and development.We assessed the association between single nucleotide polymorphisms(SNPs)in ALKBH5 and the risk of neuroblastoma in a case-control study including 402 patients and 473 non-cancer controls.Methods:Genotyping was determined by the TaqMan method.The association between ALKBH5 polymorphisms(rs1378602 and rs8400)and the risk of neuroblastoma was evaluated using the odds ratio(OR)and 95%confidence interval(CI).Results:We found no strong association of ALKBH5 rs1378602 and rs8400 with neuroblastoma risk.Further stratification analysis by age,sex,primary site,and clinical stage showed that the rs1378602 AG/AA genotype was associated with a lower risk of neuroblastoma in males(adjusted OR=0.58,95%CI=0.35–0.97,p=0.036)and children with retroperitoneal neuroblastoma(adjusted OR=0.58,95%CI=0.34–0.98,p=0.040).Conclusions:ALKBH5 SNPs do not seem to be associated with neuroblastoma risk.More studies are required to confirm this negative result and reveal the relationship between gene polymorphisms of the m6A modifier ALKBH5 and neuroblastoma. | Qian Guan Xinxin Zhang Jiabin Liu Chunlei Zhou Jinhong Zhu Haiyan Wu Zhenjian Zhuo Jing He | 2024 | Cancer Innovation2024，3，2： | 0 |
| 19 | Improvement of histone deacetylase inhibitor efficacy by SN38 through TWIST1 suppression in synovial sarcoma显示文摘Background:Synovial sarcoma(SS)is an SS18-SSX fusion gene-driven soft tissue sarcoma with mesenchymal characteristics,associated with a poor prognosis due to frequent metastasis to a distant organ,such as the lung.Histone deacetylase(HDAC)inhibitors(HDACis)are arising as potent molecular targeted drugs,as HDACi treatment disrupts the SS oncoprotein complex,which includes HDACs,in addition to general HDACi effects.To provide further molecular evidence for the advantages of HDACi treatment and its limitations due to drug resistance induced by the microenvironment in SS cells,we examined cellular responses to HDACi treatment in combination with two-dimensional(2D)and 3D culture conditions.Methods:Using several SS cell lines,biochemical and cell biological assays were performed with romidepsin,an HDAC1/2 selective inhibitor.SN38 was concomitantly used as an ameliorant drug with romidepsin treatment.Cytostasis,apoptosis induction,and MHC class I polypeptide-related sequence A/B(MICA/B)induction were monitored to evaluate the drug efficacy.In addition to the conventional 2D culture condition,spheroid culture was adopted to evaluate the influence of cell-mass microenvironment on chemoresistance.Results:By monitoring the cellular behavior with romidepsin and/or SN38 in SS cells,we observed that responsiveness is diverse in each cell line.In the apoptotic inducible cells,co-treatment with SN38 enhanced cell death.In nonapoptotic inducible cells,cytostasis and MICA/B induction were observed,and SN38 improved MICA/B induction further.As a novel efficacy of SN38,we revealed TWIST1 suppression in SS cells.In the spheroid(3D)condition,romidepsin efficacy was severely restricted in TWIST1-positive cells.We demonstrated that TWIST1 downregulation restored romidepsin efficacy even in spheroid form,and concomitant SN38 treatment along with romidepsin reproduced the reaction.Conclusions:The current study demonstrated the benefits and concerns of using HDACi for SS treatment in 2D and 3D culture conditions and provided molecular evidence that concomitant treatment with SN38 can overcome drug resistance to HDACi by suppressing TWIST1 expression. | Satoru Sasagawa Jun Kumai Toru Wakamatsu Yoshihiro Yui | 2024 | Cancer Innovation2024，3，2： | 0 |
| 20 | Establishment of a humanized mouse model using steady-state peripheral blood-derived hematopoietic stem and progenitor cells facilitates screening of cancer-targeted T-cell repertoires显示文摘Background:Cancer-targeted T-cell receptor T(TCR-T)cells hold promise in treating cancers such as hematological malignancies and breast cancers.However,approaches to obtain cancer-reactive TCR-T cells have been unsuccessful.Methods:Here,we developed a novel strategy to screen for cancer-targeted TCR-T cells using a special humanized mouse model with person-specific immune fingerprints.Rare steady-state circulating hematopoietic stem and progenitor cells were expanded via three-dimensional culture of steady-state peripheral blood mononuclear cells,and then the expanded cells were applied to establish humanized mice.The human immune system was evaluated according to the kinetics of dendritic cells,monocytes,T-cell subsets,and cytokines.To fully stimulate the immune response and to obtain B-cell precursor NAML-6-and triple-negative breast cancer MDA-MB-231-targeted TCR-T cells,we used the inactivated cells above to treat humanized mice twice a day every 7 days.Then,human T cells were processed for TCRβ-chain(TRB)sequencing analysis.After the repertoires had been constructed,features such as the fraction,diversity,and immune signature were investigated.Results:The results demonstrated an increase in diversity and clonality of T cells after treatment.The preferential usage and features of TRBV,TRBJ,and the V–J combination were also changed.The stress also induced highly clonal Science and Technology,Grant/Award Number:2021C03010;Zhejiang Provincial Natural Science Foundation of China,Grant/Award Numbers:LTGY24H080003,LY21H080004 expansion.Tumor burden and survival analysis demonstrated that stress induction could significantly inhibit the growth of subsequently transfused live tumor cells and prolong the survival of the humanized mice.Conclusions:We constructed a personalized humanized mouse model to screen cancer-targeted TCR-T pools.Our platform provides an effective source of cancer-targeted TCR-T cells and allows for the design of patient-specific engineered T cells.It therefore has the potential to greatly benefit cancer treatment. | Yulin Xu Wei Shan Qian Luo Meng Zhang Dawei Huo Yijin Chen Honghu Li Yishan Ye Xiaohong Yu Yi Luo He Huang | 2024 | Cancer Innovation2024，3，3： | 0 |
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