Article
Biochemistry & Molecular Biology
Fengtian Li, Mengmeng Niu, Kewei Qin, Rongtian Guo, Yong Yi, Jing Xu, Luping Li, Siyi Xie, Mengyuan Fu, Nasi Wen, Wenting Liao, Zhi-Xiong Jim Xiao
Summary: Triple-negative breast cancer (TNBC) is an aggressive subtype with high risk of metastasis and recurrence. Breast cancer stem cells (BCSCs) are critical in development, metastasis, recurrence, and chemotherapy resistance of breast cancer. FBXL2 serves as a negative regulator of BCSCs stemness and its downregulation plays a causal role in TNBC drug resistance.
Article
Cardiac & Cardiovascular Systems
Liu Yang, Rongbo Dai, Hao Wu, Zeyu Cai, Nan Xie, Xu Zhang, Yicong Shen, Ze Gong, Yiting Jia, Fang Yu, Ying Zhao, Pinglan Lin, Chaoyang Ye, Yanhua Hu, Yi Fu, Qingbo Xu, Zhiqing Li, Wei Kong
Summary: The study identified XBP1u as a novel endogenous inhibitor of vascular calcification by interacting and promoting the degradation of beta-catenin, representing a promising target for vascular calcification treatment.
CIRCULATION RESEARCH
(2022)
Editorial Material
Oncology
Xiuning Le, Monique B. Nilsson, Jacqulyne P. Robichaux, John V. Heymach
Summary: The ARTEMIS study showed that combining the VEGF inhibitor bevacizumab with the EGFR inhibitor erlotinib can significantly improve progression-free survival in patients with EGFR mutant non-small-cell lung cancer, especially in those with brain metastases and the EGFR L858R mutation. This suggests the potential benefits of tailored use of VEGF/EGFR combinations in this patient population.
Article
Oncology
Elisa Fiorito, Patrycja Szybowska, Ellen M. Haugsten, Michal Kostas, Geir F. Oy, Antoni Wiedlocha, Sachin Singh, Sigve Nakken, Gunhild M. Maelandsmo, Jonathan A. Fletcher, Leonardo A. Meza-Zepeda, Jorgen Wesche
Summary: This study evaluated targeting strategies for the FGFR4 V550L activating mutation in rhabdomyosarcoma. The results showed that FGF401 effectively inhibited FGFR4 V550L-dependent signaling and cell proliferation. Additionally, RAS/MAPK and PI3K/AKT were identified as druggable pathways downstream of FGFR4 V550L. Furthermore, HSP90 inhibitors efficiently impeded RMS559 cell proliferation.
BRITISH JOURNAL OF CANCER
(2022)
Article
Oncology
Lei Zhu, Zhen Chen, Hongjing Zang, Songqing Fan, Jiajia Gu, Guojing Zhang, Kevin D-Y Sun, Qiming Wang, Yong He, Taofeek K. Owonikoko, Suresh S. Ramalingam, Shi-Yong Sun
Summary: Osimertinib is a promising third-generation EGFR tyrosine kinase inhibitor for NSCLC but can lead to acquired resistance. The study reveals that modulation of c-Myc plays a critical role in therapeutic efficacy and targeting c-Myc may overcome acquired resistance, providing a potential strategy for further treatment.
Article
Genetics & Heredity
Matthew R. Swiatnicki, Jonathan P. Rennhack, Mylena M. O. Ortiz, Daniel P. Hollern, Ashlee Perry, Rachel Kubiak, Sarai M. Riveria Riveria, Sandra O'Reilly, Eran R. Andrechek
Summary: The role of EGFR in lung cancer is well-described, but the control of EGFR signaling through dephosphorylation by phosphatases is not clear. This study highlights that mutations in PTPRH in non-small cell lung cancer (NSCLC) inhibit PTPRH function, resulting in aberrant EGFR activity. The findings suggest potential clinically actionable alterations using existing therapies.
Article
Biochemistry & Molecular Biology
Chia-Hung Chen, Bo-Wei Wang, Yu-Chun Hsiao, Chun-Yi Wu, Fang-Ju Cheng, Te-Chun Hsia, Chih-Yi Chen, Yihua Wang, Zhang Weihua, Ruey-Hwang Chou, Chih-Hsin Tang, Yun-Ju Chen, Ya-Ling Wei, Jennifer L. Hsu, Chih-Yen Tu, Mien-Chie Hung, Wei-Chien Huang
Summary: Upregulation of active sodium/glucose co-transporter 1 (SGLT1) was found to confer the development of acquired EGFR TKI resistance and was correlated with poorer clinical outcomes in NSCLC patients. Blockade of SGLT1 overcame this resistance by reducing glucose uptake in NSCLC cells, suggesting a potential strategy to improve the therapeutic efficacy of EGFR TKIs in NSCLC patients.
Article
Oncology
Seung Yeon Oh, You Won Lee, Eun Ji Lee, Jae Hwan Kim, YoungJoon Park, Seong Gu Heo, Mi Ra Yu, Min Hee Hong, John DaSilva, Christopher Daly, Byoung Chul Cho, Sun Min Lim, Mi Ran Yun
Summary: REGN5093-M114, a novel antibody-drug conjugate targeting MET, exhibits significant antitumor activity in EGFR-mutated non-small cell lung cancer (NSCLC) patients. Regardless of MET gene copy number, MET-overexpressed TKI-naive EGFR-mutant NSCLC cells respond to REGN5093-M114 treatment. REGN5093-M114 potently reduces tumor growth of EGFR-mutant NSCLC with PTEN loss or MET Y1230C mutation.
CLINICAL CANCER RESEARCH
(2023)
Article
Chemistry, Multidisciplinary
Mofei Huang, Donghai Xiong, Jing Pan, Qi Zhang, Shizuko Sei, Robert H. Shoemaker, Ronald A. Lubet, Luis M. Montuenga, Yian Wang, Barbara S. Slusher, Ming You
Summary: JHU083, an orally active glutamine antagonist, effectively targets EGFR-driven lung tumorigenesis by increasing T cell infiltration and reducing immune suppressive cells, enhancing the efficacy of EVax.
Article
Multidisciplinary Sciences
Adrian Campos, Facundo Ramos, Lydia Iglesias, Celia Delgado, Eva Merino, Antonio Esperilla-Munoz, Jaime Correa-Bordes, Andres Clemente-Blanco
Summary: Phosphorylation of Dna2 by the CDK stimulates resection of DNA double-strand breaks to stimulate recombinational DNA repair. Once resection has taken place, mitotically activated Cdc14 phosphatase inhibits resection by dephosphorylating Dna2 to facilitate DNA repair by homologous recombination. This study establishes a role for Cdc14 in controlling the extent of resection through Dna2 regulation and demonstrates that the accumulation of excessively long ssDNA affects the accurate repair of the broken DNA by homologous recombination.
NATURE COMMUNICATIONS
(2023)
Article
Oncology
Alessandro Di Federico, Marco Filetti, Arianna Palladini, Raffaele Giusti, Marta Piras, Andrea De Giglio, Andrea Ardizzoni, Francesco Gelsomino
Summary: EGFR gene fusions are rare in NSCLC patients, occurring mainly in young, female, non-smoker patients with frequent brain metastases. Most NGS panels cannot detect these fusions. This study reports two cases of non-smoker female NSCLC metastatic patients with EGFR-RAD51 gene fusion who responded to EGFR TKIs, with one case being the first report of response to osimertinib.
TRANSLATIONAL LUNG CANCER RESEARCH
(2022)
Article
Oncology
Min Yu, Xiaoyu Li, Xueqian Wu, Weiya Wang, Yanying Li, Yan Zhang, Shuang Zhang, Yongsheng Wang
Summary: EGFR-TKI treatment can lead to menstrual abnormalities and abnormal vaginal bleeding in premenopausal female NSCLC patients, which may be associated with decreased progesterone level, reduced EGFR activation, and tissue factor (TF) expression in endometrial tissues.
FRONTIERS IN ONCOLOGY
(2022)
Article
Oncology
Minling Gao, Yi Fu, Weiqiang Zhou, Gege Gui, Bachuchu Lal, Yunqing Li, Shuli Xia, Hongkai Ji, Charles G. Eberhart, John Laterra, Mingyao Ying
Summary: This study focuses on uncovering the key signaling pathways of EGFR/TAF, and identifies osimertinib as an effective inhibitor that can treat cancers like GBM effectively.
Review
Pharmacology & Pharmacy
Rui-Fang Dong, Miao-Lin Zhu, Ming-Ming Liu, Yi-Ting Xu, Liu-Liu Yuan, Jing Bian, Yuan-Zheng Xia, Ling-Yi Kong
Summary: The article discusses the mechanisms of EGFR-TKIs resistance induced by secondary EGFR mutations, such as T790M and C797S. It highlights the development of targeted drugs to overcome resistance mediated by EGFR mutations.
PHARMACOLOGICAL RESEARCH
(2021)
Article
Chemistry, Medicinal
Hui Deng, Qian Lei, Weidong Shang, Ying Li, Liyun Bi, Na Yang, Zhiyi Yu, Weimin Li
Summary: This study describes the design, synthesis, and application of clickable probes for visualizing EGFR activity in cancer cells and tissues. The probes showed high reactivity and selectivity for EGFR kinase, allowing for the discrimination of EGFR mutations and prediction of EGFR-TKI therapy response.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Tingting An, Zhiming Zhang, Yuhuang Li, Jianqiao Yi, Wenhua Zhang, Deshi Chen, Juan Ao, Zhi-Xiong Xiao, Yong Yi
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2019)
Article
Biochemistry & Molecular Biology
Peng Zeng, Shengnan Sun, Rui Li, Zhi-Xiong Xiao, Hu Chen
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2019)
Article
Agriculture, Multidisciplinary
Luxi Chen, Yue Zhang, Hu Chen, Xumeng Zhang, Xiaohong Liu, Zuyong He, Peiqing Cong, Yaosheng Chen, Delin Mo
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2019)
Article
Biochemistry & Molecular Biology
Yang Wang, Juan Li, Ya Gao, Yue Luo, Hong Luo, Liang Wang, Yong Yi, Zengqiang Yuan, Zhi-Xiong Jim Xiao
Article
Multidisciplinary Sciences
Yong Yi, Deshi Chen, Juan Ao, Wenhua Zhang, Jianqiao Yi, Xiaokun Ren, Junjie Fei, Fengtian Li, Mengmeng Niu, Hu Chen, Yangkun Luo, Zhijun Luo, Zhi-Xiong Jim Xiao
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2020)
Article
Cell Biology
Shengnan Sun, Hu Chen, Lijuan Sun, Miao Wang, Xianqiang Wu, Zhi-Xiong Jim Xiao
CELL DEATH & DISEASE
(2020)
Article
Oncology
Fengtian Li, Qingyong Hu, Tao He, Jing Xu, Yong Yi, Siyi Xie, Liangping Ding, Mengyuan Fu, Rongtian Guo, Zhi-Xiong Jim Xiao, Mengmeng Niu
Article
Biology
Guohui Gao, Jie Chen, Dongbo Wang, Qiao Li, Xiaojiao Yang, Jindan Wang, Zhiyong Pan, Zhi-Xiong Jim Xiao, Yong Yi
Summary: The activation of TGF-beta signaling is crucial in promoting cancer cell migration and metastasis. TGF-beta 1 promotes degradation of Delta Np63 alpha protein to facilitate cancer metastasis and inhibits TAp63 alpha protein stability, leading to increased pancreatic cancer cell migration. Lysosomal degradation plays an important role in regulating TAp63 alpha protein fate, highlighting the significance of the TGF-beta 1-TAp63 alpha-mutant p53 axis in pancreatic cancer metastasis.
Article
Biochemistry & Molecular Biology
Xiaozhen Dai, Kai Wang, Jiawei Fan, Hanjie Liu, Xia Fan, Qian Lin, Yuhang Chen, Hu Chen, Yao Li, Hairong Liu, Oscar Chen, Jing Chen, Xiaohong Li, Di Ren, Ji Li, Daniel J. Conklin, Kupper A. Wintergerst, Yu Li, Lu Cai, Zhongbin Deng, Xiaoqing Yan, Yi Tan
Summary: Endothelial progenitor cells (EPCs) are reduced in number and impaired in function in diabetic patients. The expression of Nrf2 and its downstream genes were also decreased in EPCs from diabetic patients and db/db mice. Knockdown of Nrf2 increased apoptosis and impaired tube formation in EPCs, while Nrf2 overexpression decreased apoptosis and rescued tube formation. Mechanistic studies demonstrated that diabetes induced mitochondrial fragmentation and dysfunction of EPCs, which was attenuated by upregulating Nrf2 expression. Further analysis showed that Nrf2 specifically upregulated the transcription of IDH2 and improving mitochondrial function. Overall, Nrf2 is a potential therapeutic target for improving diabetic EPC function.
Article
Multidisciplinary Sciences
Juan Li, Yang Wang, Yue Luo, Yang Liu, Yong Yi, Jinsong Li, Yang Pan, Weiyuxin Li, Wanbang You, Qingyong Hu, Zhiqiang Zhao, Yujun Zhang, Yang Cao, Lingqiang Zhang, Junying Yuan, Zhi-Xiong Jim Xiao
Summary: This study reveals that oncogene-induced senescence (OIS) occurs infrequently in malignant adenocarcinomas in Kras-driven lung cancer. The activation of the USP5-Beclin 1 axis enhances MDM2-mediated p53 degradation to overcome senescence. The loss of Beclin 1 inhibits lung tumor growth in a mouse model. Moreover, KRAS activates USP5 by elevating ROS levels, leading to the stabilization and activation of Beclin 1 to suppress p53-dependent senescence.
NATURE COMMUNICATIONS
(2022)
Article
Oncology
Shengnan Sun, Yong Yi, Zhi-Xiong Jim Xiao, Hu Chen
Summary: Colorectal cancer (CRC) is the fourth most common cancer and p53 mutations are present in 43% of CRC cases. This study found that ER stress can induce apoptosis in p53 null colon cancer cells through the upregulation of TAp73a protein. The PERK-ATF4 signaling pathway is involved in ER stress-induced TAp73a expression and the promotion of colon cancer cell apoptosis. Therefore, targeting prolonged ER stress or upregulation of TAp73a may be a potential therapeutic strategy for colon cancer.
Article
Oncology
Tao Lv, Hong Lv, Junjie Fei, Yajun Xie, Daqing Lian, Jiang Hu, Lizhou Tang, Xiaodong Shi, Jianling Wang, Shibo Zhang, Fengtian Li, Xianjie Jiang, Yong Yi
Review
Oncology
Yong Yi, Wenhua Zhang, Jianqiao Yi, Zhi-Xiong Xiao