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RARRES2 regulates lipid metabolic reprogramming to mediate the development of brain metastasis in triple negative breast cancer

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Military Medical research 2024年第1期11卷 34-49页

作者： Yi-Qun Li Fang-Zhou Sun Chun-Xiao Li Hong-Nan Mo Yan-Tong Zhou Dan Lv Jing-Tong Zhai Hai-Li Qian Fei Ma Department of Medical oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China State Key Laboratory of Molecular oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China

Background Triple negative breast cancer(TNBC),the most aggressive subtype of breast cancer,is characterized by a high inc.dence of brain metastasis(BrM)and a poor *** the most lethal form of breast cancer,BrM remains a major clinical challenge due to its rising inc.dence and lack of effective treatment *** evidence suggested a potential role of lipid metabolic reprogramming in breast cancer brain metastasis(BCBrM),but the underlying mechanisms are far from being fully *** Through analysis of BCBrM transcriptome data from mice and patients,and immunohistochemical validation on patient tissues,we identified and verified the specific down-regulation of retinoic acid receptor responder 2(RARRES2),a multifunctional adipokine and chemokine,in BrM of *** investigated the effect of aberrant RARRES2 expression of BrM in both in vitro and in vivo *** signaling pathway components were evaluated using multi-omics *** were performed to elucidate the regulation of lipid metabolic reprogramming of *** We found that downregulation of RARRES2 is specifically associated with BCBrM,and that RARRES2 deficiency promoted BCBrM through lipid metabolic ***,reduced expression of RARRES2 in brain metastatic potential TNBC cells resulted in inc.eased levels of glycerophospholipid and decreased levels of triacylglycerols by regulating phosphatase and tensin homologue(PTEN)-mammalian target of rapamycin(mTOR)-sterol regulatory element-binding protein 1(SREBP1)signaling pathway to facilitate the survival of breast cancer cells in the unique brain *** Our work uncovers an essential role of RARRES2 in linking lipid metabolic reprogramming and the development of ***2-dependent metabolic functions may serve as potential biomarkers or therapeutic targets for BCBrM.

关键词： RARRES2 Lipid metabolic reprogramming Brain metastasis(BrM) Breast cancer

Single-cell transcriptomics reveals tumor landscape in ovarian carcinosarcoma

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2024年第8期25卷 686-699页

作者： Junfen XU Mengyan TU Department of Gynecologic oncology Women’s HospitalZhejiang University School of MedicineHangzhou 310006China Zhejiang Provinc.al clinical research Center for Obstetrics and Gynecology Hangzhou 310006China

Objective:The present study used single-cell RNA sequencing(scRNA-seq)to characterize the cellular composition of ovarian carcinosarcoma(OCS)and identify its molecular ***:scRNA-seq was performed in resected primary OCS for an in-depth analysis of tumor cells and the tumor *** staining was used for *** scRNA-seq data of OCS were compared with those of high-grade serous ovarian carcinoma(HGSOC)tumors and other OCS ***:Both malignant epithelial and malignant mesenchymal cells were observed in the OCS patient of this *** identified four epithelial cell subclusters with different biological *** them,epithelial subcluster 4 presented high levels of breast cancer type 1 susceptibility protein homolog(BRCA1)and DNA topoisomerase 2-α(TOP2A)expression and was related to drug resistance and cell *** analyzed the interaction between epithelial and mesenchymal cells and found that fibroblast growth factor(FGF)and pleiotrophin(PTN)signalings were the main pathways contributing to communication between these ***,we compared the malignant epithelial and mesenchymal cells of this OCS tumor with our previous published HGSOC scRNA-seq data and OCS *** the epithelial subclusters in the OCS tumor could be found in the HGSOC ***,the mesenchymal subcluster C14 exhibited specific expression patterns in the OCS tumor,characterized by elevated expression of cytochrome P450 family 24 subfamily A member 1(CYP24A1),collagen type XXIIIα1 chain(COL23A1),cholecystokinin(CCK),bone morphogenetic protein 7(BMP7),PTN,Wnt inhibitory factor 1(WIF1),and insulin-like growth factor 2(IGF2).Moreover,this subcluster showed distinc. characteristics when compared with both another previously published OCS tumor and normal ovarian ***:This study provides the single-cell transcriptomics signature of human OCS,which constitutes a new resource for elucidating OCS diversity.

关键词： Ovarian carcinosarcoma Single-cell RNA sequencing(scRNA-seq) Tumor heterogeneity

Development of antibody-drug conjugates in cancer:Overview and prospects

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Cancer Communications 2024年第1期44卷 3-22页

作者： Dan-Yun Ruan Hao-Xiang Wu Qi Meng Rui-Hua Xu Department of clinical research Sun Yat-sen University Cancer CenterState Key Laboratory of Oncology in South ChinaGuangdong Provincial Clinical Research Center for CancerSun Yat-sen UniversityGuangzhouGuangdongP.R.China research Unit of Precision Diagnosis and Treatment for Gastrointestinal Cancer Chinese Academy of Medical SciencesGuangzhouGuangdongP.R.China Department of Medical oncology Sun Yat-sen University Cancer CenterState Key Laboratory of Oncology in South ChinaGuangdong Provincial Clinical Research Center for CancerSun Yat-sen UniversityGuangzhouGuangdongP.R.China

In recent years,remarkable breakthroughs have been reported on antibody-drug conjugates(ADCs),with 15 ADCs successfully entering the market over the past *** substantial development has positioned ADCs as one of the fastest-growing domains in the realm of anticancer drugs,demonstrating their efficacy in treating awide array of ***,there is still an unmet clin-ical need forwider application,better efficacy,and fewer side effects of *** ADC generally comprises an antibody,a linker and a payload,and the combina-tion has profound effects on drug structure,pharmacokinetic profile and ***,optimization of the key components provides an opportunity to develop ADCs with higher potency and fewer side *** this review,we comprehen-sively reviewed the current development and the prospects of ADC,provided an analysis of marketed ADCs and the ongoing pipelines globally as well as in China,highlighted several ADC platforms and technologies specific to different pharmaceutical enterprises and biotech companies,and also discussed the new related technologies,possibility of next-generation ADCs and the directions of clinical research.

关键词： companies breakthrough payload

Gastric cancer secreted miR 214-3p inhibits the anti-angiogenesis effect of apatinib by suppressing ferroptosis in vascular endothelial cells

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oncology research 2024年第3期32卷 489-502页

作者： WEIXUE WANG TONGTONG WANG YAN ZHANG TING DENG HAIYANG ZHANG YI BA Department of GI Medical oncology Tanjin Medical University Cancer Institute and HospitalNational Clinical Research Center for CancerTianjin's Clinical Research Center for CancerTianjin Key Iaboratory of Digestive CancerKey Laboratory of Cancer Prevention and TherapyTianjin300060China

Diferent from necrosis,apoptosis,autophagy and other forms of cell death,ferroptosis is a mechanism that catalyzes lipid peroxidation of polyunsaturated ftty acids under the action of iron divalent or lipoxygenase,leading to cell *** is currently used in the third line standard treatment of advanced gastric cancer,targeting the anti-angiogenesis ***,Apatinib mediated ferroptosis in vascular endothelial cells has not been reported *** exosomes can be taken up into target cells to regulate tumor development,but the mechanism related to vascular endothelial cell ferroptosis has not yet been ***,we show that exosomes secreted by gastric cancer cells carry miR-214.3p into vascular endothelial cells and directdy target zinc.finger protein A20 to negatively regulate ACSL4,a key enzyme of lipid peroxidation during frroptosis thereby inhibiting ferroptosis in vascular endothelial cells and reducing the eficiency of *** conclusion,inhibition of miR-214-3p can inc.ease the sensitivity of vascular endothelial cells to Apatinib,thereby promoting the antiangiogenic efect of Apatinib,suggesting a potential combination therapy for advanced gastric cancer.

关键词： Cellular ferroptosis Exosome Tyrosine kinase inhibitor Gastrointestinal tumors miRNA

Microbiota in colorectal cancer related to liver metastasis

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Chinese Journal of Cancer research 2024年第1期36卷 17-24页

作者： Peijun Wei Weiming Han Zitong Zhang Xue Tian Chen Yang Qiaoxuan Wang Weihao Xie Ying Liu Yuanhong Gao Hui Chang Department of Radiation oncology State Key Laboratory of Oncology in South ChinaGuangzhou 510060China Guangdong Provinc.al clinical research Center for Cancer Guangzhou 510060China Sun Yat-sen University Cancer Center Guangzhou 510060China Department of Pediatric oncology State Key Laboratory of Oncology in South ChinaGuangzhou 510060China

The prevalence of colorectal cancer(CRC) is inc.easing annually and metastasis is the princ.pal cause of death in patients with CRC, with the liver being the most frequently affected site. Many studies have shown a strong interplay between the gut flora, particularly Fusobacterium nucleatum(F. nucleatum), Escherichia coli, and Bacteroides fragilis, and the development of gut tumors. Some strains can induce gut inflammation and produce toxins that directly harm gut epithelial cells, ultimately accelerating the onset and progression of CRC. However,little clinical evidence exists on the specific interplay between the gut microflora and colorectal cancer liver metastasis(CRLM). Some research showed the existence of viable F. nucleatum in distant metastasis of ***, gut microbiota products, such as lipopolysaccharides, sodium butyrate, and protein cathepsin K, were also found to affect the development of CRC. This article summarizes the mechanism and research status of the interplay between gut microflora and CRLM, discusses the importance of gut microflora in the treatment of CRLM, and proposes a new approach to understanding the mechanism of CRLM and potential treatments for the microbiome. It is anticipated that the gut microbiota will be a formidable therapeutic and prophylactic tool for treating and preventing CRLM.

关键词： Gut microbiota liver metastasis colorectal cancer

Pan-cancer immunogenic death analysis identifies key roles of CXCR3 and CCL18 in hepatocellular carcinoma

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Genes & Diseases 2024年第2期11卷 568-570页

作者： Jia Guo Xin Sun Guowei Pan Ce Li Xin He Xiaofang Che Zan Teng Xiujuan Qu Yunpeng Liu Bowen Yang Department of Medical oncology Provincial Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning ProvinceLiaoning Provincial Clinical Research Center for CancerClinical Cancer Research Center of ShenyangThe First Hospital of China Medical UniversityShenyangLiaoning 110001China research Center for Universal Health School of Public HealthChina Medical UniversityShenyangLiaoning 110122China

Immunogenic death is a form of programmed cell death that is common in the development and progression of ***,its impact on tumor progression differs depending on the location of the ***,it also plays an important role in antitumor immunity because the process of immunogenic death can release substances that activate immunity.1 Therefore,in this study,the key mechanism of mediating immunogenic death in hepatocellular carcinoma(HCC)was found from the excavation of the immunogenic death characteristics of pan-cancer and the in-depth investigation of its effects on different tumor types(Fig.1A).

关键词： death CXCR3 immunity

Exploring treatment options in cancer: Tumor treatment strategies

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Signal Transduction and Targeted Therapy 2024年第8期9卷 3337-3380页

作者： Beilei Liu Hongyu Zhou Licheng Tan Kin To Hugo Siu Xin-Yuan Guan Department of clinical oncology The University of Hong Kong-Shenzhen HospitalShenzhenChina Department of clinical oncology The University of Hong KongHong KongChina state Key Laboratory for Liver research The University of Hong KongHong KongChina Advanced Energy Science and Technology Guangdong Laboratory HuizhouChina MOE Key Laboratory of Tumor Molecular Biology Jinan UniversityGuangzhouChina

Traditional therapeutic approaches such as chemotherapy and radiation therapy have burdened cancer patients with onerous physical and psychological ***,the landscape of tumor treatment has undergone a comprehensive and remarkable *** as fervently pursued modalities are small molecule targeted agents,antibody-drug conjugates(ADCs),cell-based therapies,and gene *** cutting-edge treatment modalities not only afford personalized and precise tumor targeting,but also provide patients with enhanced therapeutic comfort and the potential to impede disease ***,it is acknowledged that these therapeutic strategies still harbour untapped potential for further *** a comprehensive understanding of the merits and limitations of these treatment modalities holds the promise of offering novel perspectives for clinical practice and foundational research *** this review,we discussed the different treatment modalities,inc.uding small molecule targeted drugs,peptide drugs,antibody drugs,cell therapy,and gene *** will provide a detailed explanation of each method,addressing their status of development,clinical challenges,and potential *** aim is to assist clinicians and researchers in gaining a deeper understanding of these diverse treatment options,enabling them to carry out effective treatment and advance their research more effciently.

关键词： drugs treatment holds

Transdermal treatment for malignant melanoma by aptamer-modified tetrahedral framework nucleic acid delivery of vemurafenib

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Chinese Chemical Letters 2024年第4期35卷 260-267页

作者： Dexuan Xiao Tianyu Chen Tianxu Zhang Sirong Shi Mei Zhang Xin Qin Yunkun Liu Longjiang Li Yunfeng Lin State Key Laboratory of Oral Diseases National Clinical Research Center for Oral DiseasesWest China Hospital of StomatologySichuan UniversityChengdu 610041China Sichuan Provinc.al Engineering research Center of Oral Biomaterials Chengdu 610041China Department of Head and Neck oncology National Clinical Research Center for Oral DiseasesWest China Hospital of StomatologySichuan UniversityChengdu 610041China

Melanoma is one of the most malignant skin tumors, whose high invasion is generally associated with BRAF gene mutation. Although new chemotherapeutic drugs, such as vemurafenib, have been developed to inhibit the growth of melanoma, these drugs are usually administered intravenously or orally, resulting in toxic side effects on major tissues and organs. Tetrahedral framework nucleic acids(tFNAs) are a novel type of DNA nanostructures with excellent biocompatibility and versatility which have been proven to penetrate through skin barrier with ease. In this study, we prepared t FNAs with vemurafenib and connected DNA aptamer AS1411 at the apex of t FNAs(AS1411-tFNAs/vemurafenib). On one hand, AS1411-tFNAs/vemurafenib could kill melanoma cells by blocking the mutated BRAF gene in vitro. Compared with free vemurafenib, AS1411-tFNAs/vemurafenib had no obvious toxicity to normal cells. On the other hand,AS1411-tFNAs could transfer vemurafenib to cross through the skin barrier and permeate into tumor tissues. In vivo, transdermal delivery of AS1411-t FNAs/vemurafenib could inhibit the growth of human A375melanoma, whose inhibiting effect was stronger than intravenous administration of vemurafenib. These results demonstrated the application prospects of tFNAs combined with chemotherapeutic drugs in skin tumors.

关键词： Melanoma Vemurafenib DNA nanostructure Transdermal treatment Side effect

Immune checkpoint inhibitor-associated gastritis:Patterns and management

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World Journal of Gastroenterology 2024年第14期30卷 1941-1948页

作者： Jing Lin Zhong-Qiao Lin Shi-Cheng Zheng Yu Chen Department of Medical oncology Clinical Oncology School of Fujian Medical UniversityFujian Cancer HospitalFuzhou 350000Fujian ProvinceChina Phase I clinical Trial Ward Clinical Oncology School of Fujian Medical UniversityFujian Cancer HospitalFuzhou 350000Fujian ProvinceChina School of Basic Medical Sciences Fujian Medical UniversityFuzhou 350000Fujian ProvinceChina

Immune checkpoint inhibitors(ICIs)are widely used due to their effectiveness in treating various ***-related adverse events(irAEs)are defined as adverse effects resulting from ICI *** irAEs are a common type of irAEs characterized by intestinal side effects,such as diarrhea and colitis,which may lead to the cessation of *** irAE gastritis is rarely reported,it may lead to serious complications such as ***,irAE gastritis is often difficult to identify early due to its diverse *** steroid hormones and immunosuppressants are commonly used to reverse irAEs,the best regimen and dosage for irAE gastritis remains *** addition,the risk of recurrence of irAE gastritis after the reuse of ICIs should be *** this editorial,strategies such as early identification,pathological diagnosis,mana-gement interventions,and immunotherapy rechallenge are discussed to enable clinicians to better manage irAE gastritis and improve the prognosis of these patients.

关键词： Immunotherapy Immune checkpoint inhibitor Immune-related adverse events Immune checkpoint inhibitor-related gastritis