Oncogenesis最新文献_第10页

CDK4/6 inhibitors and the pRB-E2F1 axis suppress PVR and PD-L1 expression in triple-negative breast cancer. CDK4/6抑制剂和pRB-E2F1轴抑制三阴性乳腺癌中PVR和PD-L1的表达。

IF 6.2 2区医学

Oncogenesis Pub Date : 2023-05-26 DOI: 10.1038/s41389-023-00475-1

Mariusz Shrestha, Dong-Yu Wang, Yaacov Ben-David, Eldad Zacksenhaus

{"title":"CDK4/6 inhibitors and the pRB-E2F1 axis suppress PVR and PD-L1 expression in triple-negative breast cancer.","authors":"Mariusz Shrestha, Dong-Yu Wang, Yaacov Ben-David, Eldad Zacksenhaus","doi":"10.1038/s41389-023-00475-1","DOIUrl":"https://doi.org/10.1038/s41389-023-00475-1","url":null,"abstract":"Immune-checkpoint (IC) modulators like the poliovirus receptor (PVR) and programmed death ligand 1 (PD-L1) attenuate innate and adaptive immune responses and are potential therapeutic targets for diverse malignancies, including triple-negative breast cancer (TNBC). The retinoblastoma tumor suppressor, pRB, controls cell growth through E2F1-3 transcription factors, and its inactivation drives metastatic cancer, yet its effect on IC modulators is contentious. Here, we show that RB-loss and high E2F1/E2F2 signatures correlate with expression of PVR, CD274 (PD-L1 gene) and other IC modulators and that pRB represses whereas RB depletion and E2F1 induce PVR and CD274 in TNBC cells. Accordingly, the CDK4/6 inhibitor, palbociclib, suppresses both PVR and PD-L1 expression. Palbociclib also counteracts the effect of CDK4 on SPOP, leading to its depletion, but the overall effect of palbociclib is a net reduction in PD-L1 level. Hydrochloric acid, commonly used to solubilize palbociclib, counteracts its effect and induces PD-L1 expression. Remarkably, lactic acid, a by-product of glycolysis, also induces PD-L1 as well as PVR. Our results suggest a model in which CDK4/6 regulates PD-L1 turnover by promoting its transcription via pRB-E2F1 and degradation via SPOP and that the CDK4/6-pRB-E2F pathway couples cell proliferation with the induction of multiple innate and adaptive immunomodulators, with direct implications for cancer progression, anti-CDK4/6- and IC-therapies.","PeriodicalId":19489,"journal":{"name":"Oncogenesis","volume":"12 1","pages":"29"},"PeriodicalIF":6.2,"publicationDate":"2023-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10213015/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9531118","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 4

Phosphorylation of IWS1 by AKT maintains liposarcoma tumor heterogeneity through preservation of cancer stem cell phenotypes and mesenchymal-epithelial plasticity. AKT磷酸化IWS1通过维持肿瘤干细胞表型和间充质上皮可塑性来维持脂肪肉瘤肿瘤的异质性。

IF 6.2 2区医学

Oncogenesis Pub Date : 2023-05-26 DOI: 10.1038/s41389-023-00469-z

Yu Wang, Hongji Zhang, Alessandro La Ferlita, Nipin Sp, Marina Goryunova, Patricia Sarchet, Zhiwei Hu, Michael Sorkin, Alex Kim, Hai Huang, Hua Zhu, Allan Tsung, Raphael E Pollock, Joal D Beane

{"title":"Phosphorylation of IWS1 by AKT maintains liposarcoma tumor heterogeneity through preservation of cancer stem cell phenotypes and mesenchymal-epithelial plasticity.","authors":"Yu Wang, Hongji Zhang, Alessandro La Ferlita, Nipin Sp, Marina Goryunova, Patricia Sarchet, Zhiwei Hu, Michael Sorkin, Alex Kim, Hai Huang, Hua Zhu, Allan Tsung, Raphael E Pollock, Joal D Beane","doi":"10.1038/s41389-023-00469-z","DOIUrl":"https://doi.org/10.1038/s41389-023-00469-z","url":null,"abstract":"Chemotherapy remains the mainstay of treatment for patients with advanced liposarcoma (LPS), but response rates are only 25% and the overall survival at 5 years is dismal at 20-34%. Translation of other therapies have not been successful and there has been no significant improvement in prognosis for nearly 20 years. The aberrant activation of the phosphatidylinositol 3-kinase (PI3K)/AKT pathway has been implicated in the aggressive clinical behavior LPS and in resistance to chemotherapy, but the precise mechanism remains elusive and efforts to target AKT clinically have failed. Here we show that the AKT-mediated phosphorylation of the transcription elongation factor IWS1, promotes the maintenance of cancer stem cells in both cell and xenograft models of LPS. In addition, phosphorylation of IWS1 by AKT contributes to a \"metastable\" cell phenotype, characterized by mesenchymal/epithelial plasticity. The expression of phosphorylated IWS1 also promotes anchorage-dependent and independent growth, cell migration, invasion, and tumor metastasis. In patients with LPS, IWS1 expression is associated with reduced overall survival, increased frequency of recurrence, and shorter time to relapse after resection. These findings indicate that IWS1-mediated transcription elongation is an important regulator of human LPS pathobiology in an AKT-dependent manner and implicate IWS1 as an important molecular target to treat LPS.","PeriodicalId":19489,"journal":{"name":"Oncogenesis","volume":"12 1","pages":"30"},"PeriodicalIF":6.2,"publicationDate":"2023-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10219984/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9902904","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

Circlehunter: a tool to identify extrachromosomal circular DNA from ATAC-Seq data. Circlehunter:从ATAC-Seq数据中识别染色体外环状DNA的工具。

IF 6.2 2区医学

Oncogenesis Pub Date : 2023-05-22 DOI: 10.1038/s41389-023-00476-0

Manqiu Yang, Shufan Zhang, Rong Jiang, Shaomu Chen, Moli Huang

{"title":"Circlehunter: a tool to identify extrachromosomal circular DNA from ATAC-Seq data.","authors":"Manqiu Yang, Shufan Zhang, Rong Jiang, Shaomu Chen, Moli Huang","doi":"10.1038/s41389-023-00476-0","DOIUrl":"https://doi.org/10.1038/s41389-023-00476-0","url":null,"abstract":"In cancer, extrachromosomal circular DNA (ecDNA), or megabase-pair amplified circular DNA, plays an essential role in intercellular heterogeneity and tumor cell revolution because of its non-Mendelian inheritance. We developed circlehunter ( https://github.com/suda-huanglab/circlehunter ), a tool for identifying ecDNA from ATAC-Seq data using the enhanced chromatin accessibility of ecDNA. Using simulated data, we showed that circlehunter has an F1 score of 0.93 at 30× local depth and read lengths as short as 35 bp. Based on 1312 ecDNAs predicted from 94 publicly available datasets of ATAC-Seq assays, we found 37 oncogenes contained in these ecDNAs with amplification characteristics. In small cell lung cancer cell lines, ecDNA containing MYC leads to amplification of MYC and cis-regulates the expression of NEUROD1, resulting in an expression pattern consistent with the NEUROD1 high expression subtype and sensitive to Aurora kinase inhibitors. This showcases that circlehunter could serve as a valuable pipeline for the investigation of tumorigenesis.","PeriodicalId":19489,"journal":{"name":"Oncogenesis","volume":"12 1","pages":"28"},"PeriodicalIF":6.2,"publicationDate":"2023-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10202962/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9516110","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 2

Correction: USP53 plays an antitumor role in hepatocellular carcinoma through deubiquitination of cytochrome c. 更正:USP53通过去泛素化细胞色素c在肝癌中发挥抗肿瘤作用。

IF 6.2 2区医学

Oncogenesis Pub Date : 2023-05-15 DOI: 10.1038/s41389-023-00470-6

Ye Yao, Weijie Ma, Yonghua Guo, Yingyi Liu, Peng Xia, Xiaoling Wu, Yiran Chen, Kunlei Wang, Chengjie Mei, Ganggang Wang, Xiaomian Li, Zhonglin Zhang, Xi Chen, Yufeng Yuan

引用次数: 0

Dual role of ANGPTL8 in promoting tumor cell proliferation and immune escape during hepatocarcinogenesis. 肝癌发生过程中ANGPTL8在促进肿瘤细胞增殖和免疫逃逸中的双重作用。

IF 6.2 2区医学

Oncogenesis Pub Date : 2023-05-15 DOI: 10.1038/s41389-023-00473-3

Yujiu Gao, Yue Yuan, Shu Wen, Yanghui Chen, Zongli Zhang, Ying Feng, Bin Jiang, Shinan Ma, Rong Hu, Chen Fang, Xuzhi Ruan, Yahong Yuan, Xinggang Fang, Chao Luo, Zhongji Meng, Xiaoli Wang, Xingrong Guo

{"title":"Dual role of ANGPTL8 in promoting tumor cell proliferation and immune escape during hepatocarcinogenesis.","authors":"Yujiu Gao, Yue Yuan, Shu Wen, Yanghui Chen, Zongli Zhang, Ying Feng, Bin Jiang, Shinan Ma, Rong Hu, Chen Fang, Xuzhi Ruan, Yahong Yuan, Xinggang Fang, Chao Luo, Zhongji Meng, Xiaoli Wang, Xingrong Guo","doi":"10.1038/s41389-023-00473-3","DOIUrl":"https://doi.org/10.1038/s41389-023-00473-3","url":null,"abstract":"The interplay between hepatocellular carcinoma (HCC) cells and the tumor microenvironment is essential for hepatocarcinogenesis, but their contributions to HCC development are incompletely understood. We assessed the role of ANGPTL8, a protein secreted by HCC cells, in hepatocarcinogenesis and the mechanisms through which ANGPTL8 mediates crosstalk between HCC cells and tumor-associated macrophages. Immunohistochemical, Western blotting, RNA-Seq, and flow cytometry analyses of ANGPTL8 were performed. A series of in vitro and in vivo experiments were conducted to reveal the role of ANGPTL8 in the progression of HCC. ANGPTL8 expression was positively correlated with tumor malignancy in HCC, and high ANGPTL8 expression was associated with poor overall survival (OS) and disease-free survival (DFS). ANGPTL8 promoted HCC cell proliferation in vitro and in vivo, and ANGPTL8 KO inhibited the development of HCC in both DEN-induced and DEN-plus-CCL4-induced mouse HCC tumors. Mechanistically, the ANGPTL8-LILRB2/PIRB interaction promoted polarization of macrophages to the immunosuppressive M2 phenotype in macrophages and recruited immunosuppressive T cells. In hepatocytes, ANGPTL8-mediated stimulation of LILRB2/PIRB regulated the ROS/ERK pathway and upregulated autophagy, leading to the proliferation of HCC cells. Our data support the notion that ANGPTL8 has a dual role in promoting tumor cell proliferation and immune escape during hepatocarcinogenesis.","PeriodicalId":19489,"journal":{"name":"Oncogenesis","volume":"12 1","pages":"26"},"PeriodicalIF":6.2,"publicationDate":"2023-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10185523/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9539530","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

miR-137-LAPTM4B regulates cytoskeleton organization and cancer metastasis via the RhoA-LIMK-Cofilin pathway in osteosarcoma. miR-137-LAPTM4B在骨肉瘤中通过RhoA-LIMK-Cofilin通路调控细胞骨架组织和肿瘤转移。

IF 6.2 2区医学

Oncogenesis Pub Date : 2023-05-06 DOI: 10.1038/s41389-023-00471-5

Ruyu Yan, Dan Liu, Junjie Wang, Minxia Liu, Hongjuan Guo, Jing Bai, Shuo Yang, Jun Chang, Zhihong Yao, Zuozhang Yang, Tomas Blom, Kecheng Zhou

{"title":"miR-137-LAPTM4B regulates cytoskeleton organization and cancer metastasis via the RhoA-LIMK-Cofilin pathway in osteosarcoma.","authors":"Ruyu Yan, Dan Liu, Junjie Wang, Minxia Liu, Hongjuan Guo, Jing Bai, Shuo Yang, Jun Chang, Zhihong Yao, Zuozhang Yang, Tomas Blom, Kecheng Zhou","doi":"10.1038/s41389-023-00471-5","DOIUrl":"https://doi.org/10.1038/s41389-023-00471-5","url":null,"abstract":"Osteosarcoma (OS) is a rare malignant bone tumor but is one leading cause of cancer mortality in childhood and adolescence. Cancer metastasis accounts for the primary reason for treatment failure in OS patients. The dynamic organization of the cytoskeleton is fundamental for cell motility, migration, and cancer metastasis. Lysosome Associated Protein Transmembrane 4B (LAPTM4B) is an oncogene participating in various biological progress central to cancer biogenesis. However, the potential roles of LAPTM4B in OS and the related mechanisms remain unknown. Here, we established the elevated LAPTM4B expression in OS, and it is essential in regulating stress fiber organization through RhoA-LIMK-cofilin signaling pathway. In terms of mechanism, our data revealed that LAPTM4B promotes RhoA protein stability by suppressing the ubiquitin-mediated proteasome degradation pathway. Moreover, our data show that miR-137, rather than gene copy number and methylation status, contributes to the upregulation of LAPTM4B in OS. We report that miR-137 is capable of regulating stress fiber arrangement, OS cell migration, and metastasis via targeting LAPTM4B. Combining results from cells, patients' tissue samples, the animal model, and cancer databases, this study further suggests that the miR-137-LAPTM4B axis represents a clinically relevant pathway in OS progression and a viable target for novel therapeutics.","PeriodicalId":19489,"journal":{"name":"Oncogenesis","volume":"12 1","pages":"25"},"PeriodicalIF":6.2,"publicationDate":"2023-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10163001/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9797994","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 2

Vortioxetine hydrobromide inhibits the growth of gastric cancer cells in vivo and in vitro by targeting JAK2 and SRC. 沃替西汀在体内和体外通过靶向JAK2和SRC抑制胃癌细胞的生长。

IF 6.2 2区医学

Oncogenesis Pub Date : 2023-05-05 DOI: 10.1038/s41389-023-00472-4

Mingzhu Li, Lina Duan, Wenjie Wu, Wenjing Li, Lili Zhao, Ang Li, Xuebo Lu, Xinyu He, Zigang Dong, Kangdong Liu, Yanan Jiang

{"title":"Vortioxetine hydrobromide inhibits the growth of gastric cancer cells in vivo and in vitro by targeting JAK2 and SRC.","authors":"Mingzhu Li, Lina Duan, Wenjie Wu, Wenjing Li, Lili Zhao, Ang Li, Xuebo Lu, Xinyu He, Zigang Dong, Kangdong Liu, Yanan Jiang","doi":"10.1038/s41389-023-00472-4","DOIUrl":"https://doi.org/10.1038/s41389-023-00472-4","url":null,"abstract":"Gastric cancer is the fourth leading cause of cancer deaths worldwide. Most patients are diagnosed in the advanced stage. Inadequate therapeutic strategies and the high recurrence rate lead to the poor 5-year survival rate. Therefore, effective chemopreventive drugs for gastric cancer are urgently needed. Repurposing clinical drugs is an effective strategy for discovering cancer chemopreventive drugs. In this study, we find that vortioxetine hydrobromide, an FDA-approved drug, is a dual JAK2/SRC inhibitor, and has inhibitory effects on cell proliferation of gastric cancer. Computational docking analysis, pull-down assay, cellular thermal shift assay (CETSA) and in vitro kinase assays are used to illustrate vortioxetine hydrobromide directly binds to JAK2 and SRC kinases and inhibits their kinase activities. The results of non-reducing SDS-PAGE and Western blotting indicate that vortioxetine hydrobromide suppresses STAT3 dimerization and nuclear translocation activity. Furthermore, vortioxetine hydrobromide inhibits the cell proliferation dependent on JAK2 and SRC and suppresses the growth of gastric cancer PDX model in vivo. These data demonstrate that vortioxetine hydrobromide, as a novel dual JAK2/SRC inhibitor, curbs the growth of gastric cancer in vitro and in vivo by JAK2/SRC-STAT3 signaling pathways. Our results highlight that vortioxetine hydrobromide has the potential application in the chemoprevention of gastric cancer.","PeriodicalId":19489,"journal":{"name":"Oncogenesis","volume":"12 1","pages":"24"},"PeriodicalIF":6.2,"publicationDate":"2023-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10163056/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9797996","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

Retinoic acid receptor β modulates mechanosensing and invasion in pancreatic cancer cells via myosin light chain 2. 视黄酸受体β通过肌球蛋白轻链2调节胰腺癌细胞的机械传感和侵袭。

IF 6.2 2区医学

Oncogenesis Pub Date : 2023-05-02 DOI: 10.1038/s41389-023-00467-1

Carlos Matellan, Dariusz Lachowski, Ernesto Cortes, Kai Ning Chiam, Aleksandar Krstic, Stephen D Thorpe, Armando E Del Río Hernández

{"title":"Retinoic acid receptor β modulates mechanosensing and invasion in pancreatic cancer cells via myosin light chain 2.","authors":"Carlos Matellan, Dariusz Lachowski, Ernesto Cortes, Kai Ning Chiam, Aleksandar Krstic, Stephen D Thorpe, Armando E Del Río Hernández","doi":"10.1038/s41389-023-00467-1","DOIUrl":"https://doi.org/10.1038/s41389-023-00467-1","url":null,"abstract":"Pancreatic ductal adenocarcinoma (PDAC) is the most common and lethal form of pancreatic cancer, characterised by stromal remodelling, elevated matrix stiffness and high metastatic rate. Retinoids, compounds derived from vitamin A, have a history of clinical use in cancer for their anti-proliferative and differentiation effects, and more recently have been explored as anti-stromal therapies in PDAC for their ability to induce mechanical quiescence in cancer associated fibroblasts. Here, we demonstrate that retinoic acid receptor β (RAR-β) transcriptionally represses myosin light chain 2 (MLC-2) expression in pancreatic cancer cells. As a key regulatory component of the contractile actomyosin machinery, MLC-2 downregulation results in decreased cytoskeletal stiffness and traction force generation, impaired response to mechanical stimuli via mechanosensing and reduced ability to invade through the basement membrane. This work highlights the potential of retinoids to target the mechanical drivers of pancreatic cancer.","PeriodicalId":19489,"journal":{"name":"Oncogenesis","volume":"12 1","pages":"23"},"PeriodicalIF":6.2,"publicationDate":"2023-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10154384/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9465718","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 3

Anti-PD-1 therapy achieves favorable outcomes in HBV-positive non-liver cancer. 抗pd -1治疗在hbv阳性非肝癌中取得了良好的效果。

IF 6.2 2区医学

Oncogenesis Pub Date : 2023-04-20 DOI: 10.1038/s41389-023-00468-0

Jie Zhou, Guanming Chen, Jiuling Wang, Bo Zhou, Xuemin Sun, Jinsong Wang, Shu Tang, Xiangju Xing, Xiaofei Hu, Yang Zhao, Yu Peng, Wenjiong Shi, Tingting Zhao, Yuzhang Wu, Hanbing Zhong, Ni Hong, Zhihua Ruan, Yi Zhang, Wenfei Jin

{"title":"Anti-PD-1 therapy achieves favorable outcomes in HBV-positive non-liver cancer.","authors":"Jie Zhou, Guanming Chen, Jiuling Wang, Bo Zhou, Xuemin Sun, Jinsong Wang, Shu Tang, Xiangju Xing, Xiaofei Hu, Yang Zhao, Yu Peng, Wenjiong Shi, Tingting Zhao, Yuzhang Wu, Hanbing Zhong, Ni Hong, Zhihua Ruan, Yi Zhang, Wenfei Jin","doi":"10.1038/s41389-023-00468-0","DOIUrl":"https://doi.org/10.1038/s41389-023-00468-0","url":null,"abstract":"Anti-PD-1 therapy has shown promising outcomes in the treatment of different types of cancer. It is of fundamental interest to analyze the efficacy of anti-PD-1 therapy in cancer patients infected with hepatitis B virus (HBV) since the comorbidity of HBV and cancer is widely documented. We designed a multicenter retrospective study to evaluate the efficacy of anti-PD-1 therapy on non-liver cancer patients infected with HBV. We found anti-PD-1 therapy achieved much better outcomes in HBV+ non-liver cancer patients than their HBV- counterparts. We performed single-cell RNA sequencing (scRNA-seq) on peripheral blood mononuclear cells (PBMCs) from esophageal squamous cell carcinoma (ESCC) patients. We found both cytotoxicity score of T cells and MHC score of B cells significantly increased after anti-PD-1 therapy in HBV+ ESCC patients. We also identified CX3CR1high TEFF, a subset of CD8+ TEFF, associated with better clinical outcome in HBV+ ESCC patients. Lastly, we found CD8+ TEFF from HBV+ ESCC patients showing higher fraction of Exhaustionhi T than their HBV- counterpart. In summary, anti-PD-1 therapy on HBV+ non-liver cancer patients is safe and achieves better outcomes than that on HBV- non-liver cancer patients, potentially because HBV+ patients had higher fraction of Exhaustionhi T, which made them more efficiently respond to anti-PD-1 therapy.","PeriodicalId":19489,"journal":{"name":"Oncogenesis","volume":"12 1","pages":"22"},"PeriodicalIF":6.2,"publicationDate":"2023-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10119302/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9476763","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Exploring potential molecular resistance and clonal evolution in advanced HER2-positive gastric cancer under trastuzumab therapy. 曲妥珠单抗治疗晚期her2阳性胃癌的潜在分子耐药和克隆进化

IF 6.2 2区医学

Oncogenesis Pub Date : 2023-04-18 DOI: 10.1038/s41389-023-00466-2

Qi Xu, Xiaoqing Xu, Haimeng Tang, Junrong Yan, Jingjing Li, Hua Bao, Xue Wu, Yang Shao, Cong Luo, Haimin Wen, Jianying Jin, Jieer Ying

{"title":"Exploring potential molecular resistance and clonal evolution in advanced HER2-positive gastric cancer under trastuzumab therapy.","authors":"Qi Xu, Xiaoqing Xu, Haimeng Tang, Junrong Yan, Jingjing Li, Hua Bao, Xue Wu, Yang Shao, Cong Luo, Haimin Wen, Jianying Jin, Jieer Ying","doi":"10.1038/s41389-023-00466-2","DOIUrl":"https://doi.org/10.1038/s41389-023-00466-2","url":null,"abstract":"HER2-positive gastric cancer (GC) makes up 15-20% of all GC incidences, and targeted therapy with trastuzumab is the standard of treatment. However, the mechanisms of resistance to trastuzumab are still not fully understood and presents a significant challenge in clinical practice. In this study, whole exome sequencing (WES) was performed on paired tumor tissues before trastuzumab treatment (at baseline) and at progressive disease (PD) in 23 GC patients. Clinicopathological and molecular features that may be associated with primary and/or acquired resistance to trastuzumab were identified. Lauren classification of intestinal type was associated with a more prolonged progression-free survival (PFS) than diffuse type (HR = 0.29, P = 0.019). Patients with low tumor mutation burden (TMB) showed significantly worse PFS, while high chromosome instability (CIN) was correlated with prolonged OS (HR = 0.27; P = 0.044). Patients who responded to treatment had a higher CIN than nonresponders, and a positive trend towards increasing CIN was observed as response improved (P = 0.019). In our cohort, the most common genes to acquire mutations are AURKA, MYC, STK11, and LRP6 with four patients each. We also discovered an association between clonal branching pattern and survival, with an extensive clonal branching pattern being more closely related to a shorter PFS than other branching patterns (HR = 4.71; P = 0.008). We identified potential molecular and clinical factors that provide insight regarding potential association to trastuzumab resistance in advanced HER2-positive GC patients.","PeriodicalId":19489,"journal":{"name":"Oncogenesis","volume":"12 1","pages":"21"},"PeriodicalIF":6.2,"publicationDate":"2023-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10113330/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9412891","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1