Article
Biochemistry & Molecular Biology
Ji Hye Kim, Jongwook Kim, Se Seul Im, Ji Hyeon Lee, Sein Hwang, Eun-Ju Chang, Dong-Myung Shin, Jin Kyung Rho, Jaekyoung Son
Summary: The research found that BIX induces apoptotic cell death in EGFR-mutant NSCLC cells and inhibits EGFR signaling, especially in EGFR-TKI resistant cells.
EXPERIMENTAL AND MOLECULAR MEDICINE
(2021)
Article
Chemistry, Medicinal
Hong-Yi Zhao, Hai-Peng Wang, Yu-Ze Mao, Hao Zhang, Minhang Xin, Xiao-Xiao Xi, Hao Lei, Shuai Mao, Dong-Hui Li, San-Qi Zhang
Summary: This study developed proteolysis targeting chimeras (PROTACs) targeting EGFR mutants by optimizing covalent EGFR ligands to overcome drug resistance in non-small-cell lung cancer (NSCLC). The covalent PROTAC CP17 was discovered to be a highly potent degrader against EGFRL858R/T790M and EGFRdel19 with excellent selectivity. Mechanism investigation showed that the lysosome was involved in the degradation process. Importantly, the covalent binding strategy was proven to be effective for designing PROTACs targeting EGFRL858R/T790M.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Pharmacology & Pharmacy
Po-Yen Chen, Chin-Chou Wang, Chien-Ning Hsu, Chung-Yu Chen
Summary: This study compared the relative survival rate of gefitinib, erlotinib, and afatinib in EGFR-mutated advanced lung adenocarcinoma patients in Taiwan. Afatinib showed better overall survival and time to treatment failure outcomes compared to gefitinib and erlotinib, especially in patients with initial brain metastases.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Wei Feng, Xi Chen, Shao-xing Guan, Hong-lian Ruan, Yan Huang, Hui-zhen Zhang, Yun-peng Yang, Wen-feng Fang, Hong-yun Zhao, Wei Zhuang, Shuang Xin, You-hao Chen, Fei Wang, Yue Gao, Min Huang, Xue-ding Wang, Li Zhang
Summary: For NSCLC patients with EGFR sensitive mutations, the standard dose of gefitinib may be too high and could potentially be decreased for better efficacy. The metabolite M2 plays a significant role in efficacy and may be more effective in the treatment of metastatic tumors compared to gefitinib.
ACTA PHARMACOLOGICA SINICA
(2022)
Article
Oncology
Yuki Katayama, Tadaaki Yamada, Shinsaku Tokuda, Naoko Okura, Naoya Nishioka, Kenji Morimoto, Keiko Tanimura, Yoshie Morimoto, Masahiro Iwasaku, Mano Horinaka, Toshiyuki Sakai, Kenji Kita, Seiji Yano, Koichi Takayama
Summary: EGFR-T790M mutation is a major mechanism of acquired resistance to EGFR-TKIs in lung cancer. The biological characteristics of T790M tumors differ based on treatment regimens with each generation of EGFR-TKI. The maintenance of EGFR dependency after acquiring resistance may depend on the type of EGFR-TKI.
Article
Cell Biology
Zenghua Sheng, Xu Cao, Ya-nan Deng, Xinyu Zhao, Shufang Liang
Summary: This study reveals that SUMOylation modification of the EGFR-binding protein AnxA6 plays a crucial role in regulating epithelial cancer cell growth and the effectiveness of gefitinib.
CELL COMMUNICATION AND SIGNALING
(2023)
Article
Medicine, Research & Experimental
Shigeki Nanjo, Wei Wu, Niki Karachaliou, Collin M. Blakely, Junji Suzuki, Yu-Ting Chou, Siraj M. Ali, D. Lucas Kerr, Victor R. Olivas, Jonathan Shue, Julia Rotow, Manasi K. Mayekar, Franziska Haderk, Nilanjana Chatterjee, Anatoly Urisman, Jia Chi Yeo, Anders J. Skanderup, Aaron C. Tan, Wai Leong Tam, Oscar Arrieta, Kazuyoshi Hosomichi, Akihiro Nishiyama, Seiji Yano, Yuriy Kirichok, Daniel S. W. Tan, Rafael Rosell, Ross A. Okimoto, Trever G. Bivona
Summary: This study investigates the impact of co-occurring genetic alterations on mutant EGFR and identifies the deficiency of RNA-binding factor RBM10 as a factor that decreases the efficacy of EGFR inhibitors in lung cancer treatment. The study reveals that RBM10 modulates tumor cell apoptosis by regulating the alternative splicing of Bcl-x and its deficiency diminishes EGFR inhibitor-mediated apoptosis. The findings suggest that co-occurring genetic alterations and splicing factor deficiency play a role in determining the sensitivity to targeted kinase inhibitor therapy.
JOURNAL OF CLINICAL INVESTIGATION
(2022)
Article
Cell Biology
Carolien Eggermont, Philippe Giron, Maxim Noeparast, Hugo Vandenplas, Pedro Aza-Blanc, Gustavo J. Gutierrez, Jacques De Greve
Summary: In this study, a high-throughput siRNA kinome screen was performed to identify targets involved in functional drug tolerance against EGFR TKI in NSCLC. STYK1 was identified as a potential target that, when downregulated, enhances the effects of EGFR inhibition. The study also found that STYK1 selectively interacts with mutant EGFR and that its downregulation counteracts the upregulation of FGF1 induced by EGFR TKI. Co-targeting EGFR and STYK1 could lead to a better overall outcome for NSCLC patients.
CELL DEATH & DISEASE
(2022)
Article
Oncology
Huihui Guo, Xilin Zhang, Shangzhi Xie, Tianwei Chen, Dong Xie, Ying Cai, Dawei Cui, Liang Wang, Wei Chen, Xiang Wang
Summary: This study discovered a new mechanism of action of gefitinib in EGFR-mutated NSCLC cells, involving the regulation of B7H5/CD28H axis expression, which enhanced the cytotoxicity of immune cells against NSCLC cells. This provides new insights into the immune evasion mechanism mediated by EGFR mutations and identifies potential targets for immune therapy.
INTERNATIONAL JOURNAL OF ONCOLOGY
(2022)
Article
Chemistry, Medicinal
Yasheng Zhu, Xiuquan Ye, Hao Shen, Jiaxing Li, Zeyu Cai, Wenjian Min, Yi Hou, Haojie Dong, Yuxing Wu, Liping Wang, Xiao Wang, Yibei Xiao, Peng Yang
Summary: In this study, a novel EGFR inhibitor targeting Osimertinib resistance was identified by virtual screening and compound synthesis. The representative compound showed potent antitumor activity and good pharmacokinetic properties and oral bioavailability.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Oncology
Qing Zhou, Lin Wu, Pei Hu, Tongtong An, Jianying Zhou, Li Zhang, Xiao-Qing Liu, Feng Luo, Xin Zheng, Ying Cheng, Nong Yang, Junling Li, Jifeng Feng, Baohui Han, Yong Song, Kai Wang, Jian Fang, Hong Zhao, Yongqian Shu, Xiao-Yan Lin, Zhihong Chen, Bin Gan, Wan-Hong Xu, Wei Tang, Xiaoying Zhang, Jin-Ji Yang, Xiao Xu, Yi-Long Wu
Summary: Abivertinib at a dose of 300 mg twice a day demonstrated favorable clinical efficacy with manageable side effects in patients with EGFR T790M(+) NSCLC.
CLINICAL CANCER RESEARCH
(2022)
Article
Oncology
Chunsheng Wang, Kewei Zhao, Shanliang Hu, Wei Dong, Yan Gong, Minghuan Li, Conghua Xie
Summary: By studying the outcomes of gefitinib and erlotinib in patients with uncommon EGFR mutations in non-small cell lung cancer (NSCLC), it was found that patients with compound mutations had better treatment response, with those containing exon 19 deletion or L858R mutations showing the most significant benefits in response and survival. Additionally, the gefitinib group showed superior treatment efficacy and PFS benefit compared to the erlotinib group.
Article
Oncology
Sanjay Popat, Te-Chun Hsia, Jen-Yu Hung, Hyun Ae Jung, Jin-Yuan Shih, Cheol Kyu Park, Seung Hyeun Lee, Tatsuro Okamoto, Hee Kyung Ahn, Yong Chul Lee, Yuki Sato, Sung Sook Lee, Celine Mascaux, Hasan Daoud, Angela Marten, Satoru Miura
Summary: This article presents findings from the UpSwinG study on the efficacy of EGFR TKI treatment in patients with uncommon EGFR mutations. The study shows that in a real-world setting, EGFR TKIs are the preferred treatment option for patients with uncommon EGFR mutations, with strongest outcomes observed in patients with major uncommon and compound mutations.
Article
Cell Biology
Wei Wei, Shuishe Zhang, Hui Han, Xiaoche Wang, Siyi Zheng, Zhaoyu Wang, Chunlong Yang, Lu Wang, Jieyi Ma, Siyao Guo, Juan Wang, Lianlian Liu, Junho Choe, Shuibin Lin
Summary: The upregulated expression of NAT10 is associated with poor prognosis in esophageal cancer. NAT10 plays a critical role in promoting esophageal cancer tumorigenesis and progression by regulating ac4C-modified tRNAs and mRNA translation. EGFR is identified as a downstream target of NAT10 that facilitates its oncogenic functions. Additionally, the depletion of NAT10 and the treatment with ge-fitinib synergistically inhibit esophageal cancer progression, suggesting potential therapeutic strategies.
Article
Biochemistry & Molecular Biology
Fang-Ju Cheng, Chia-Hung Chen, Wen-Chen Tsai, Bo-Wei Wang, Meng-Chieh Yu, Te-Chun Hsia, Ya-Ling Wei, Yu-Chun Hsiao, Dai-Wei Hu, Chien-Yi Ho, Tzong-Shiun Li, Chun-Yi Wu, Wen-Yu Chou, Yung-Luen Yu, Chih-Hsin Tang, Chih-Yi Chen, Chuan-Mu Chen, Jennifer L. Hsu, Hsiao-Fan Chen, Yeh Chen, Chih-Yen Tu, Mien-Chie Hung, Wei-Chien Huang
Summary: Smokers with non-small cell lung cancer have lower sensitivity to EGFR tyrosine kinase inhibitors, as exposure to cigarette smoke extract enhances glycolysis and weakens the inhibition of mTOR by AMPK, thus reducing the sensitivity of NSCLC cells to EGFR TKI by repressing LKB1 expression. Additionally, LKB1 expression is positively correlated with TKI sensitivity in NSCLC patients, and combined treatment with EGFR TKI and AMPK activators increases TKI sensitivity synergistically.
Article
Biochemical Research Methods
Kei Irie, Saori Shobu, Seika Hiratsuji, Yuta Yamasaki, Shigeki Nanjo, Chiyuki Kokan, Akito Hata, Reiko Kaji, Katsuhiro Masago, Shiro Fujita, Yutaka Okada, Nobuyuki Katakami, Shoji Fukushima
JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES
(2018)
Article
Oncology
Katsuhiro Masago, Kei Irie, Shiro Fujita, Fumiko Imamichi, Yutaka Okada, Nobuyuki Katakami, Shoji Fukushima, Yasushi Yatabe
Article
Pathology
Katsuhiro Masago, Shiro Fujita, Akito Hata, Chiyuki Okuda, Yuko Yoshizumi, Reiko Kaji, Nobuyuki Katakami, Yukio Hirata, Yasushi Yatabe
PATHOLOGY INTERNATIONAL
(2018)
Editorial Material
Respiratory System
Katsuhiro Masago, Shiro Fujita, Yasushi Yatabe
JOURNAL OF THORACIC DISEASE
(2018)
Article
Pathology
Katsutoshi Seto, Masataka Haneda, Katsuhiro Masago, Shiro Fujita, Seiichi Kato, Eiichi Sasaki, Waki Hosoda, Yoshiko Murakami, Hiroaki Kuroda, Yoshitsugu Horio, Toyoaki Hida, Kenichi Okubo, Yasushi Yatabe
PATHOLOGY INTERNATIONAL
(2020)
Editorial Material
Oncology
Katsuhiro Masago, Yoshitsugu Horio, Shiro Fujita, Yasushi Yatabe
TRANSLATIONAL LUNG CANCER RESEARCH
(2019)
Article
Oncology
Katsutoshi Seto, Katsuhiro Masago, Shiro Fujita, Masataka Haneda, Yoshitsugu Horio, Toyoaki Hida, Hiroaki Kuroda, Waki Hosoda, Ken-ichi Okubo
Letter
Oncology
Eiichi Sasaki, Katsuhiro Masago, Shiro Fujita, Michi Sawabe, Nobuhiro Hanai, Waki Hosoda
Article
Multidisciplinary Sciences
Shiro Fujita, Katsuhiro Masago
Summary: This study aimed to clarify the genetic factors contributing to the co-occurrence of non-small-cell lung cancer and nonmedullary thyroid cancer. Through germline exome sequencing in a cohort of patients and target resequencing on candidate genes, rare missense heterozygous variants in MSH6 and MLH1 were identified. The findings suggest a causal role of impaired DNA mismatch repair capacity in these malignancies.
SCIENTIFIC REPORTS
(2021)
Letter
Pathology
Eiichi Sasaki, Akari Iwakoshi, Katsuhiro Masago, Nobuhiro Hanai, Masahide Oki
Article
Oncology
Katsutoshi Seto, Junichi Shimizu, Katsuhiro Masago, Mitsugu Araki, Ryohei Katayama, Yukari Sagae, Shiro Fujita, Yoshitsugu Horio, Eiichi Sasaki, Hiroaki Kuroda, Kenichi Okubo, Yasushi Okuno, Toyoaki Hida
Summary: In this study, the sensitivity of BRAF tyrosine kinase inhibitor mechanism in patients with rare BRAF compound mutation was clarified and predicted using genetic analysis and computational simulation model. The results demonstrated the importance of constructing a genomic and simulation fused database for the development of personalized medicine in this field.
Article
Medicine, General & Internal
Katsuhiro Masago, Shiro Fujita, Yuko Oya, Yusuke Takahashi, Hirokazu Matsushita, Eiichi Sasaki, Hiroaki Kuroda
Summary: This study compared the QubitTM and NanoDropTM methods for quantification, finding that NanoDropTM measured higher DNA concentrations but not for RNA. The success rate of genomic tests using DNA samples below the QubitTM detection limit was as high as 96%, while the success rate for RNA tests was lower.
MEDICINA-LITHUANIA
(2021)
Article
Pathology
Eiichi Sasaki, Katsuhiro Masago, Shiro Fujita, Nobuhiro Hanai, Yasushi Yatabe
JOURNAL OF PATHOLOGY CLINICAL RESEARCH
(2020)
Article
Nursing
Katsuhiro Masago, Fumiko Imamichi, Yoshio Masuda, Noriko Ariga, Kiyomi Fujitomi, Yoko Fukumine, Kana Hatakenaka, Shiro Fujita, Nobuyuki Katakami
ASIA-PACIFIC JOURNAL OF ONCOLOGY NURSING
(2018)
Article
Oncology
Toyoaki Hida, Makoto Nishio, Naoyuki Nogami, Yuichiro Ohe, Hiroshi Nokihara, Hiroshi Sakai, Miyako Satouchi, Kazuhiko Nakagawa, Mitsuhiro Takenoyama, Hiroshi Isobe, Shiro Fujita, Hiroshi Tanaka, Koichi Minato, Toshiaki Takahashi, Makoto Maemondo, Koji Takeda, Hideo Saka, Koichi Goto, Shinji Atagi, Tomonori Hirashima, Naoki Sumiyoshi, Tomohide Tamura