Article
Oncology
Yong Du, Yongfeng Chen, Yuxia Wang, Jinju Chen, Xiaorong Lu, Li Zhang, Yan Li, Zhaofu Wang, Guozhong Ye, George Zhang
Summary: HJM-561 is an orally bioavailable EGFR PROTAC that selectively degrades EGFR C797S-containing triple mutants, showing promising therapeutic option for overcoming drug resistance in NSCLC.
MOLECULAR CANCER THERAPEUTICS
(2022)
Article
Multidisciplinary Sciences
Juliann Chmielecki, Jhanelle E. Gray, Ying Cheng, Yuichiro Ohe, Fumio Imamura, Byoung Chul Cho, Meng-Chih Lin, Margarita Majem, Riyaz Shah, Yuri Rukazenkov, Alexander Todd, Aleksandra Markovets, J. Carl Barrett, Ryan J. Hartmaier, Suresh S. Ramalingam
Summary: By sequencing circulating tumor DNA in patients from the FLAURA trial, this study identifies MET amplification and EGFR C797S mutation as the most frequent acquired resistance mechanisms to first-line osimertinib.
NATURE COMMUNICATIONS
(2023)
Article
Oncology
Steven W. W. Criscione, Matthew J. J. Martin, Derek B. B. Oien, Aparna Gorthi, Ricardo J. J. Miragaia, Jingwen Zhang, Huawei Chen, Daniel L. L. Karl, Kerrin Mendler, Aleksandra Markovets, Sladjana Gagrica, Oona Delpuech, Jonathan R. R. Dry, Michael Grondine, Maureen M. M. Hattersley, Jelena Urosevic, Nicolas Floc'h, Lisa Drew, Yi Yao, Paul D. D. Smith
Summary: This study characterized osimertinib drug tolerant persister (DTP) cells using RNA-seq and ATAC-seq, and identified vulnerabilities in these cells through drug screening. Several common vulnerabilities were linked to gene regulatory changes, and were further validated using genetic approaches.
NPJ PRECISION ONCOLOGY
(2022)
Article
Chemistry, Medicinal
Haojie Dong, Xiuquan Ye, Yasheng Zhu, Hao Shen, Hongtao Shen, Weijiao Chen, Minghui Ji, Mingming Zheng, Keren Wang, Zeyu Cai, Haopeng Sun, Yibei Xiao, Peng Yang
Summary: In this study, a series of Osimertinib derivatives were designed as fourth-generation inhibitors targeting Osimertinib-resistant NSCLC. The top candidate D51 showed potent inhibition against EGFR mutants, selectivity against wild-type forms, and favorable in vivo druggability.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Oncology
Kentaro Tanaka, Hajime Asahina, Junji Kishimoto, Yoshihiro Miyata, Takahiro Uchida, Kana Watanabe, Kosuke Hamai, Taishi Harada, Yukari Tsubata, Shunichi Sugawara, Kunihiko Kobayashi, Kenji Sugio, Satoshi Oizumi, Isamu Okamoto
Summary: The study investigated the combination of osimertinib with cytotoxic chemotherapy for EGFR-mutated NSCLC patients, finding that adding chemotherapy as a second-line treatment did not prolong survival but was generally well-tolerated.
EUROPEAN JOURNAL OF CANCER
(2021)
Review
Oncology
Kai Fu, Fachao Xie, Fang Wang, Liwu Fu
Summary: Osimertinib is an effective treatment for advanced NSCLC patients with EGFR mutations, but acquired resistance limits its efficacy. This article comprehensively summarizes the resistance mechanisms of osimertinib and discusses potential therapeutic strategies for EGFR-mutated NSCLC patients.
JOURNAL OF HEMATOLOGY & ONCOLOGY
(2022)
Article
Oncology
Kai Lu, Hsin-Chiao Wang, Yi-Chen Tu, Cheng-Chung Chang, Pei-Jen Lou, Ta-Chau Chang, Jing-Jer Lin
Summary: In this study, the G-quadruplex ligand BMVC-8C3O was shown to suppress acquired resistance to osimertinib in non-small cell lung cancer cells. Combination treatment of BMVC-8C3O and osimertinib had a synergistic inhibitory effect on the growth of resistant tumors both in vitro and in vivo.
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
(2023)
Article
Oncology
Julie A. Vendrell, Xavier Quantin, Audrey Aussel, Isabelle Solassol, Isabelle Serre, Jerome Solassol
Summary: The study suggests that ctDNA NGS analysis can rapidly select appropriate drugs after osimertinib failure and predict clinical outcomes of patients. Patients who develop EGFR-dependent resistance respond better to osimertinib and have a more favorable clinical outcome.
TRANSLATIONAL LUNG CANCER RESEARCH
(2021)
Article
Oncology
James Chih-Hsin Yang, Yuichiro Ohe, Chao -Hua Chiu, Xiaoling Ou, Mireille Cantarini, Pasi A. Janne, Ryan J. Hartmaier, Myung Ju Ahn
Summary: The combination of osimertinib and selumetinib showed promising antitumor activity and tolerability in patients with MET-negative, EGFRm advanced NSCLC who had progressed on previous EGFR-TKI treatment.
CLINICAL CANCER RESEARCH
(2022)
Review
Oncology
Yan Chen, Zijun Chen, Rui Chen, Cheng Fang, Chu Zhang, Mei Ji, Xin Yang
Summary: The rapid development of molecular targeted therapy brings hope to patients with advanced non-small-cell lung cancer. However, drug resistance occurs during EGFR-TKI treatment. Osimertinib shows a favorable prognosis, but acquired resistance is still a challenge. PD-1 and PD-L1 inhibitors have made progress, especially in patients with no actionable mutations. This review summarizes the relationship between EGFR mutations and PD-L1 expression and important clinical studies on immunotherapy-inhibitor-based treatment in EGFR-TKI-resistant NSCLC patients.
Editorial Material
Oncology
Sun Min Lim, Chang Gon Kim, Jii Bum Lee, Byoung Chul Cho
Summary: This article highlights the potential of patritumab deruxtecan as a valuable therapeutic agent for previously treated EGFR-mutant NSCLC, based on early clinical data. It emphasizes the ubiquitous expression of HER3 in EGFR-mutant NSCLC, making it an important therapeutic target.
Article
Oncology
Yan Li, Ziyi Xu, Tongji Xie, Puyuan Xing, Jianming Ying, Junling Li
Summary: EGFR mutations are important drivers of gene alterations in lung adenocarcinomas, but resistance to EGFR-TKIs is common. The heterogeneity of resistant mechanisms is closely related to the number of treatment lines. When choosing treatment options, it is important to focus on the major clone of the tumor and make timely adjustments based on the dynamic changes of genetic characteristics.
FRONTIERS IN ONCOLOGY
(2022)
Review
Genetics & Heredity
Shigetoshi Nishihara, Toshimitsu Yamaoka, Fumihiro Ishikawa, Kensuke Higuchi, Yuki Hasebe, Ryo Manabe, Yasunari Kishino, Sojiro Kusumoto, Koichi Ando, Yusuke Kuroda, Tohru Ohmori, Hironori Sagara, Hitoshi Yoshida, Junji Tsurutani
Summary: Homeostasis is achieved by balancing cell survival and death. In cancer cells, this balance is disrupted, allowing for the survival and proliferation of dysregulated cells. The mechanisms by which EGFR-TKIs induce apoptosis, a form of cell death, are not fully understood. Understanding these mechanisms is crucial for developing strategies to overcome resistance or enhance the efficacy of EGFR-TKIs in treating EGFR-mutated NSCLC.
Article
Multidisciplinary Sciences
Yoshihisa Kobayashi, Geoffrey R. Oxnard, Elizabeth F. Cohen, Navin R. Mahadevan, Joao Alessi, Yin P. Hung, Arrien A. Bertram, David E. Heppner, Mauricio F. Ribeiro, Karina P. Sacardo, Rodrigo Saddi, Mariana P. Macedo, Rafael B. Blasco, Jiaqi Li, Kari J. Kurppa, Tom Nguyen, Emma Voligny, Guruprasad Ananda, Roberto Chiarle, Artur Katz, Michael Y. Tolstorukov, Lynette M. Sholl, Pasi A. Janne
Summary: By studying EGFR inhibitor-resistant patients, the researchers identified a minority of patients carrying fusion oncogenes that can cause resistance to EGFR inhibitors. They further validated the functionality of these fusion oncogenes and identified drug resistance mechanisms to combination therapies.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Zhen Chen, Danlei Yu, Taofeek K. Owonikoko, Suresh S. Ramalingam, Shi-Yong Sun
Summary: This study has demonstrated the critical role of SREBP1 degradation in the response of EGFR mutant NSCLC cells to osimertinib, and proposed an effective strategy for overcoming acquired resistance to osimertinib by targeting SREBP1.
Article
Chemistry, Applied
Xiao-Bin Huang, Luo-Wei Yuan, Jing Shao, Yan Yang, Yi Liu, Jin-Jian Lu, Lei Chen
Summary: In this chemical study, a new flavanonol and twenty-six known compounds were isolated from the dried root of Sophora flavescens. Compound 21 showed significant cell proliferation inhibition effect on lung cancer A549 cells and colon cancer HCT116 cells, indicating potential anti-cancer activity of flavonoids from S. flavescens.
NATURAL PRODUCT RESEARCH
(2021)
Article
Pharmacology & Pharmacy
Ao Li, Xiao Xiao, Zhe-Ling Feng, Xiuping Chen, Li-Juan Liu, Li-Gen Lin, Jin-Jian Lu, Le-Le Zhang
TOXICOLOGY AND APPLIED PHARMACOLOGY
(2020)
Article
Oncology
Le-Le Zhang, Han Bao, Yu-Lian Xu, Xiao-Ming Jiang, Wei Li, Liang Zou, Li-Gen Lin, Jin-Jian Lu
ANTI-CANCER AGENTS IN MEDICINAL CHEMISTRY
(2020)
Article
Pharmacology & Pharmacy
Ting Li, Xiao-Huang Xu, Xia Guo, Tao Yuan, Zheng-Hai Tang, Xiao-Ming Jiang, Yu-Lian Xu, Le-Le Zhang, Xiuping Chen, Hong Zhu, Jia-Jie Shi, Jin-Jian Lu
BIOCHEMICAL PHARMACOLOGY
(2020)
Article
Biochemistry & Molecular Biology
Yunjun Ge, Shuo Zhang, Junlin Wang, Fangbo Xia, Jian-Bo Wan, Jinjian Lu, Richard D. Ye
Article
Biochemistry & Molecular Biology
Jie Yu, Bingling Zhong, Long Jin, Ying Hou, Nana Ai, Wei Ge, Luoxiang Li, Shuqin Liu, Jin-Jian Lu, Xiuping Chen
FREE RADICAL BIOLOGY AND MEDICINE
(2020)
Article
Chemistry, Applied
Le-Le Zhang, Mu-Yang Huang, Yong Yang, Ming-Qing Huang, Jia-Jie Shi, Liang Zou, Jin-Jian Lu
Review
Oncology
Yu-Chi Chen, Wei Shi, Jia-Jie Shi, Jin-Jian Lu
Summary: The development of CD47 targeting agents faces hematotoxicity as a common side effect, but strategies such as changing the mode of administration and using bispecific antibodies can mitigate this issue.
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Qing-Xin Ji, Fei-Yan Zeng, Jian Zhou, Wen-Bin Wu, Xu-Jie Wang, Zhen Zhang, Guo-Yan Zhang, Jie Tong, Di-Yang Sun, Jia-Bao Zhang, Wen-Xiang Cao, Fu-Ming Shen, Jin-Jian Lu, Dong-Jie Li, Pei Wang
Summary: This study explores the potential role of ferroptosis in smooth muscle cell (SMC) phenotypic switch and neointimal formation. It found that ferroptotic stress is triggered in dedifferentiated SMCs and arterial neointimal tissue. Inhibition of ferroptosis delays SMC phenotype switch and arterial remodeling, while ferroptosis stress directly triggers SMC dedifferentiation.
CELL DEATH AND DIFFERENTIATION
(2023)
Article
Biochemistry & Molecular Biology
Min-Hui Chen, Fong Leong, Si-Jia Gao, Xin Chen, Jin-Jian Lu, Li-Gen Lin, Yitao Wang, Xiao-Jia Chen
Summary: A reliable method was developed for the simultaneous determination of nine chemical components in Chuanmaidong, Zhemaidong, and SMD, and significant differences in their contents were found. The anticancer effects of Chuanmaidong and Zhemaidong extracts were stronger than those of SMD.
Review
Pharmacology & Pharmacy
Zi-Han Ye, Wei-Bang Yu, Mu-Yang Huang, Jun Chen, Jin-Jian Lu
Summary: This review discusses the clinical and preclinical cases of combination therapies targeting CD47, explores their mechanisms of action, and shares ideas for the future.
ACTA PHARMACEUTICA SINICA B
(2023)
Article
Oncology
Ziyou Lin, Jingwei Li, Jian Zhang, Weineng Feng, Jiaye Lu, Xiaofan Ma, Wen Ding, Shumin Ouyang, Jinjian Lu, Peibin Yue, Guohui Wan, Peiqing Liu, Xiaolei Zhang
Summary: Acquired resistance is a bottleneck for targeted therapy in lung cancer, and metabolic adaptation may contribute to it. This study discovered a novel mechanism of acquired resistance to EGFR tyrosine kinase inhibitors mediated by IGF2BP3-dependent cross-talk between epigenetic modifications and metabolic reprogramming. IGF2BP3 upregulation is associated with reduced overall survival in TKI-resistant non-small cell lung cancer patients.
Article
Pathology
Xin-Yuan Li, Xin-Yu He, Hong Zhao, Lu Qi, Jin-Jian Lu
Summary: This study identified MRPL9 as an upregulated gene in lung cancer tissues, which was associated with poor prognosis. Knockdown of MRPL9 inhibited lung cancer cell proliferation, sphere formation, and migration ability. MRPL9 was associated with the c-MYC signaling pathway and its co-expression with MYC correlated with a worse prognosis in lung cancer patients. Bioinformatics analysis revealed the association between c-MYC and the EMT regulator ZEB1. Interfering with c-MYC expression confirmed the relationship between ZEB1 and c-MYC. Thus, MRPL9 may serve as a potential therapeutic target for lung cancer by affecting c-MYC and regulating ZEB1.
PATHOLOGY RESEARCH AND PRACTICE
(2023)
Article
Oncology
Xin-Ling He, Wen-Yu Lyu, Xin-Yuan Li, Hong Zhao, Lu Qi, Jin-Jian Lu
Summary: Traditional Chinese medicine (TCM) has been used widely in cancer treatment. This study identifies glycogen phosphorylase L (PYGL) as a targeted protein for TCMs in various cancer types, with its expression level correlated with lung cancer stage and poor prognosis. Knockdown of PYGL inhibits proliferation and migration in lung cancer cells. PYGL is also associated with cellular components related to mitosis in lung cancer and is susceptible to upregulation by mutated genes. Therefore, PYGL is a potential target for lung cancer treatment, influencing cellular mitotic function through energy metabolism regulation.
Article
Biochemistry & Molecular Biology
Nan Yao, Chen-Ran Wang, Ming-Qun Liu, Ying-Jie Li, Wei-Min Chen, Zheng-Qiu Li, Qi Qi, Jin-Jian Lu, Chun-Lin Fan, Min-Feng Chen, Ming Qi, Xiao-Bo Li, Jian Hong, Dong-Mei Zhang, Wen-Cai Ye
SIGNAL TRANSDUCTION AND TARGETED THERAPY
(2020)
Review
Oncology
Xinru Zhou, Yin Jia, Chuanbin Mao, Shanrong Liu
Summary: Small extracellular vesicles (sEVs), such as exosomes, have emerged as crucial targets for liquid biopsy and promising drug delivery vehicles in tumor progression. They can serve as biomarkers for tumor diagnosis and as drug carriers for cancer treatment.
Article
Oncology
Ruochan Chen, Ju Zhu, Xiao Zhong, Jie Li, Rui Kang, Daolin Tang
Summary: The interplay between autophagy and apoptosis plays a crucial role in tumorigenesis and cancer therapy, with HMGB1 serving as a key regulator in these processes.
Article
Oncology
Zongfu Pan, Xixuan Lu, Tong Xu, Jinming Chen, Lisha Bao, Ying Li, Yingying Gong, Yulu Che, Xiaozhou Zou, Zhuo Tan, Ping Huang, Minghua Ge
Summary: This study uncovered the emerging role of HN1 in promoting dedifferentiation of anaplastic thyroid cancer (ATC) cells. HN1 negatively regulated the thyroid differentiation markers and had an inhibitory effect on the transcriptional activation of CTCF, thereby influencing the chromatin accessibility of thyroid differentiation genes.
Article
Oncology
Yi Qin, Shengjun Xiong, Jun Ren, Gautam Sethi
Summary: Autophagy plays an important regulatory role in glioblastoma, and its dysregulation can lead to drug resistance and radioresistance. It also affects stem cell characteristics, overall growth, and metastasis. Therefore, autophagy is a promising target for glioblastoma therapy.
Article
Oncology
Katsuya Nagaoka, Xuewei Bai, Dan Liu, Kevin Cao, Joud Mulla, Chengcheng Ji, Hongze Chen, Muhammad Azhar Nisar, Amalia Bay, William Mueller, Grace Hildebrand, Jin-Song Gao, Shaolei Lu, Hiroko Setoyama, Yasuhito Tanaka, Jack R. Wands, Chiung-Kuei Huang
Summary: This study found that serum 2-OG levels in cholangiocarcinoma patients are associated with the effectiveness of chemotherapy. Patients with progressive disease showed significantly higher levels of serum 2-OG compared to stable disease and partial response patients. The study also revealed that overexpression of ASPH mimics the effects of 2-OG, and knockdown of ASPH improves chemotherapy. Targeting ASPH enhances the effects of chemotherapy by modulating ATM and ATR, two key regulators of DDRs.
