Review
Immunology
Fenge Li, Huancheng Wu, Xueming Du, Yimo Sun, Barbara Nassif Rausseo, Amjad Talukder, Arjun Katailiha, Lama Elzohary, Yupeng Wang, Zhiyu Wang, Gregory Lizee
Summary: The EGFR gene is frequently overexpressed and mutated in various solid tumors, and peptide vaccines targeting mutated EGFR have shown promising clinical efficacy and safety profiles.
Review
Oncology
Julia Lai-Kwon, Crescens Tiu, Abhijit Pal, Sachin Khurana, Anna Minchom
Summary: EGFR mutations are the most common targetable oncogenic driver mutation in metastatic non-small lung cancer. The development of third-generation inhibitor osimertinib has shown improved outcomes compared to first and second generation agents. Despite excellent initial response rates, responses may not be durable due to the development of acquired resistance, highlighting the importance of understanding resistance mechanisms and exploring drug combinations.
CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY
(2021)
Article
Cell Biology
Zhe Liu, Liang Ma, Yiming Sun, Wenying Yu, Xue Wang
Summary: The study demonstrated that the STAT3/ZEB1 axis is critical in gefitinib resistance in lung cancer, and a new potential therapeutic strategy targeting STAT3 has been identified with the inhibitor LL1. LL1 was shown to sensitize resistant cells to gefitinib by depleting STAT3 activity and blocking its signaling pathways, with little observed toxicity in animal models, indicating it could be a chemotherapeutic adjuvant for gefitinib resistance in NSCLC.
CELL DEATH & DISEASE
(2021)
Article
Oncology
Zofia Piotrowska, Daniel Shao-Weng Tan, Egbert F. Smit, Alexander I. Spira, Ross A. Soo, Danny Nguyen, Victor Ho-Fun Lee, James Chih-Hsin Yang, Vamsidhar Velcheti, John M. Wrangle, Mark A. Socinski, Marianna Koczywas, John E. Janik, Jeffrey Jones, Helena Alexandra Yu
Summary: This study demonstrates that Zipalertinib has encouraging antitumor activity in heavily pretreated patients with EGFR ex20ins-mutant NSCLC, with an acceptable safety profile and low frequency of high-grade diarrhea and rash.
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Article
Immunology
How-Wen Ko, Shian-Sen Shie, Chih-Wei Wang, Chi-Tsun Chiu, Chih-Liang Wang, Tsung-Ying Yang, Shou-Chu Chou, Chien-Ying Liu, Chih-Hsi Scott Kuo, Yu-Ching Lin, Li-Fu Li, Cheng-Ta Yang, Chin-Chou Wang
Summary: This study identifies a comprehensive spectrum of uncommon EGFR mutations and demonstrates a positive relationship between smoking status and the frequency of uncommon EGFR mutations, particularly complex uncommon EGFR mutations. The results suggest that smoking contributes to the development of complex EGFR mutations.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Oncology
Hiroshi Nokihara, Hirokazu Ogino, Atsushi Mitsuhashi, Kensuke Kondo, Ei Ogawa, Ryohiko Ozaki, Yohei Yabuki, Hiroto Yoneda, Kenji Otsuka, Yasuhiko Nishioka
Summary: These data suggest that the efficacy of osimertinib may differ between EGFR T790M-positive and -negative NSCLC patients with PE. The presence of PE was independently associated with shorter PFS and OS in EGFR T790M-positive NSCLC patients, but not in EGFR T790M-negative patients.
Article
Multidisciplinary Sciences
Chuantao Zhang, Man Jiang, Na Zhou, Helei Hou, Tianjun Li, Hongsheng Yu, Yuan-De Tan, Xiaochun Zhang
Summary: Using gene differential expression and gene ontology, a set of 26 tumor suppressor genes were identified, with SASH1, STARD13, CBFA2T3, and RECK showing strong tumor suppressor effects, and EXT1, PTCH1, KLK10, and APC demonstrating weak tumor suppressor effects. These genes can be used as specific and sensitive biomarkers for diagnosis of NSCLC cancer.
SCIENTIFIC REPORTS
(2021)
Review
Cell Biology
Emma-Anne Karlsen, Sam Kahler, Joan Tefay, Shannon R. Joseph, Fiona Simpson
Summary: This review critically analyzes the mechanisms of EGFR expression in NSCLC, its relevance to currently approved targeted treatment options, and the complex nature of secondary mutations and intrinsic and acquired resistance patterns in NSCLC.
Article
Chemistry, Medicinal
Chaofan Wang, Xiaoyun Lu
Summary: MET is a promising drug target for the treatment of MET-dependent diseases, especially NSCLC. Small molecule MET inhibitors with three types of binding modes have been developed. This review provides an overview of MET's structural features, activation mechanism, dysregulation pathway, and the development strategies of MET inhibitors, as well as the acquired resistance mechanisms. These insights will accelerate the discovery of new generation MET inhibitors to overcome clinical acquired resistance.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biology
Xiaolong Tang, Lizhi Cheng, Guo Li, Yong-Ming Yan, Fengting Su, Dan-Ling Huang, Shuping Zhang, Zuojun Liu, Minxian Qian, Ji Li, Yong-Xian Cheng, Baohua Liu
Summary: The small molecule compound D6 demonstrates promising efficacy in treating EGFR-TKI resistant NSCLC by targeting the protein-protein interaction between HSP90 and T790M-EGFR, offering a potential alternative strategy to overcome drug resistance.
COMMUNICATIONS BIOLOGY
(2021)
Article
Oncology
Wen-Qian Li, Ling-Yu Li, Jin Chai, Jiu-Wei Cui
Summary: Recent cost-effectiveness analysis showed that first-generation EGFR-TKI therapy remains the most cost-effective treatment option for advanced EGFR-mutant NSCLC patients, with potential implications for clinical practice and medical insurance reimbursement policies.
Article
Oncology
Chi-Lu Chiang, Chia- Shen, Hsu-Ching Huang, Han-Jhih Chang, Yu-Ting Huang, Chao-Hua Chiu
Summary: This study investigates the optimal approach for EGFR mutation testing in NSCLC patients using centrifuged effusion samples and proposes a cytology-based specimen triage. The proposed strategy improves the detection rate of EGFR mutations and provides an efficient testing strategy for patients with EGFR-mutant NSCLC.
FRONTIERS IN ONCOLOGY
(2022)
Article
Oncology
Hiroaki Fujii, Hideyuki Nagakura, Nobuaki Kobayashi, Sousuke Kubo, Katsushi Tanaka, Keisuke Watanabe, Nobuyuki Horita, Yu Hara, Masanori Nishikawa, Kenji Miura, Harumi Koizumi, Yu Ito, Motofumi Tsubakihara, Naoki Miyazawa, Makoto Kudo, Masaharu Shinkai, Takeshi Kaneko
Summary: This study aimed to determine the effectiveness of liquid biopsy in detecting EGFR mutations in lung cancer. The results showed that liquid biopsy detected EGFR mutations in 63.6% of the patients at diagnosis. Patients with positive EGFR mutations had shorter survival. Some patients with progressive disease had T790M mutations. The results of liquid biopsy were consistent with tissue re-biopsy.
Article
Oncology
Kensuke Kanaoka, Hiromitsu Sumikawa, Shunsuke Oyamada, Akihiro Tamiya, Yuji Inagaki, Yoshihiko Taniguchi, Keiko Nakao, Yoshinobu Matsuda, Kyoichi Okishio
Summary: This study investigated the prevalence and details of osteoblastic bone reaction (OBR) in patients with EGFR-mutant NSCLC treated with osimertinib and its association with clinical outcomes. Most patients with bone metastasis from NSCLC who received osimertinib treatment developed OBR, which should not be confused with disease progression.
Article
Biochemistry & Molecular Biology
Nidhi Saini, Ajmer Singh Grewal, Viney Lather, Suresh Kumar Gahlawat
Summary: Phytochemicals contribute to protection and interaction processes by acting as antioxidants, anti-mutagens, anticarcinogens, and antimicrobial agents. In this study, sanguinarine was found to be the most potent inhibitor of epidermal growth factor receptor (EGFR) compared to erlotinib. Other alkaloids also showed potent inhibition against EGFR, but their stability with EGFR varied. Out of the 31 alkaloids subjected to ADMET prediction, 29 alkaloids followed Lipinski's rule of five and were predicted to have high bioavailability, low toxicity, and ease of synthesis.
CHEMICO-BIOLOGICAL INTERACTIONS
(2022)
