Article
Oncology
Lingling Zhao, Zhen Wang, Haiwei Du, Songan Chen, Pingli Wang
Summary: The efficacy of EGFR-TKIs in patients with rare EGFR mutations such as EGFR-KDD remains unclear, although case reports have shown variable antitumor responses. Treatment with afatinib in a 61-year-old male with T1N3M0 LUAD harboring EGFR-KDD resulted in partial response with a progression-free survival of 12 months and counting, providing clinical evidence for EGFR-TKI administration in advanced LUAD patients with EGFR-KDD.
FRONTIERS IN ONCOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Masayuki Komatsu, Kanako Nakamura, Takashi Takeda, Fumiko Chiwaki, Kouji Banno, Daisuke Aoki, Fumitaka Takeshita, Hiroki Sasaki
Summary: This study proposes a new concept of inducing addiction to oncogenic signaling through specific blockade of target molecules. In experiments with cervical squamous cell carcinoma cells, dual blockade of Aurora A/B led to rapid addiction to EGFR-Erk signaling, and the synergistic inhibition of this signaling enhanced anti-cancer activities in vitro, in vivo, and in a patient-derived organoid model.
Article
Oncology
Ming-Ju Tsai, Jen-Yu Hung, Juei-Yang Ma, Yu-Chen Tsai, Kuan-Li Wu, Mei-Hsuan Lee, Chia-Yu Kuo, Cheng-Hao Chuang, Tai-Huang Lee, Yen-Lung Lee, Chun-Ming Huang, Mei-Chiou Shen, Chih-Jen Yang, Inn-Wen Chong
Summary: This study retrospectively enrolled patients with lung adenocarcinomas harboring EGFR mutations who were treated with first-line afatinib. Patients who received local consolidative therapy (LCT) had significantly longer PFS and OS. Multivariable analysis and propensity score-weighting showed consistent results. This study suggests that LCT may improve clinical outcomes, in terms of PFS and OS, in patients with advanced EGFR-mutant lung adenocarcinomas who are treated with first-line afatinib.
Article
Medicine, General & Internal
Dapeng Li, Qi Gui, Caihua Xu, Meng Shen, Kai Chen
Summary: In patients with EGFR mutations, the T790 M mutation may coexist with bypass pathway activation in non-small cell lung cancer. This case study highlights a patient who underwent multiple treatments for different EGFR resistance mutations and had an overall survival of 24 months.
Article
Oncology
Michael J. Grant, Jacqueline V. Aredo, Jacqueline H. Starrett, Paul Stockhammer, Iris K. van Alderwerelt van Rosenburgh, Anna Wurtz, Andrew J. Piper-Valillo, Zofia Piotrowska, Christina Falcon, Helena A. Yu, Charu Aggarwal, Dylan Scholes, Tejas Patil, Christina Nguyen, Manali Phadke, Fang -Yong Li, Joel Neal, Mark A. Lemmon, Zenta Walther, Katerina Politi, Sarah B. Goldberg
Summary: The drug osimertinib has reduced effectiveness in treating the uncommon EGFR mutation ex19del L747_A750>P compared to the common mutation E746_A750del in non-small cell lung cancer patients. The clinical efficacy of osimertinib in treating tumors with L747_A750>P and other uncommon ex19dels is not known.
CLINICAL CANCER RESEARCH
(2023)
Article
Oncology
Yuko Oya, Tatsuya Yoshida, Kazuhiro Asada, Tetsuya Oguri, Naoki Inui, Sayako Morikawa, Kentaro Ito, Tomoki Kimura, Eiji Kunii, Takashi Matsui, Akihito Kubo, Tatsuo Kato, Takashi Abe, Takeshi Tsuda, Toyoaki Hida
Summary: In patients treated with afatinib, the detection of EGFR-driver and T790M in plasma by cobas might be lower than with gefitinib/erlotinib in a real-world setting.
Article
Chemistry, Medicinal
Meredith S. Eno, Jason D. Brubaker, John E. Campbell, Chris De Savi, Timothy J. Guzi, Brett D. Williams, Douglas Wilson, Kevin Wilson, Natasja Brooijmans, Joseph Kim, Aysegul Ozen, Emanuele Perola, John Hsieh, Victoria Brown, Kristina Fetalvero, Andrew Garner, Zhuo Zhang, Faith Stevison, Rich Woessner, Jatinder Singh, Yoav Timsit, Caitlin Kinkema, Clare Medendorp, Christopher Lee, Faris Albayya, Alena Zalutskaya, Stefanie Schalm, Thomas A. Dineen
Summary: While EGFR tyrosine kinase inhibitors have revolutionized the treatment of NSCLC, the development of resistance mutations remains a challenge. This study introduces a novel reversible inhibitor, BLU-945, that shows promising activity against different resistance mutations. Clinical trials are currently underway to evaluate its efficacy and safety.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Oncology
Yu-Ra Choi, Youngnam Cho, Seog-Yun Park, Sunshin Kim, Myungsun Shin, Yongdoo Choi, Dong Hoon Shin, Ji-Youn Han, Youngjoo Lee
Summary: This study investigates the expansion of resistant cancer cells in response to EGFR inhibitors and suggests that early on-treatment kinetics of resistance-related gene alterations may predict the final mechanism of EGFR-TKI resistance. These findings provide insights into the development of EGFR-TKI resistance.
Article
Oncology
Andres F. Cardona, Daniel Jaramillo-Velasquez, Alejandro Ruiz-Patino, Carolina Polo, Enrique Jimenez, Fernando Hakim, Diego Gomez, Juan Fernando Ramon, Hernando Cifuentes, Juan Armando Mejia, Fernando Salguero, Camila Ordonez, Alvaro Munoz, Sonia Bermudez, Nicolas Useche, Diego Pineda, Luisa Ricaurte, Zyanya Lucia Zatarain-Barron, July Rodriguez, Jenny Avila, Leonardo Rojas, Elvira Jaller, Carolina Sotelo, Juan Esteban Garcia-Robledo, Nicolas Santoyo, Christian Rolfo, Rafael Rosell, Oscar Arrieta
Summary: This study targeted adult patients with recurrent GB enriched for EGFR amplification and EGFRvIII mutation, using osimertinib/bevacizumab combination therapy, and found some patients experienced long-lasting meaningful benefits. Resistance patterns after treatment included known mechanisms in EGFR regulation, contributing to understanding and targeting this pathway in a rational stepwise manner.
JOURNAL OF NEURO-ONCOLOGY
(2021)
Article
Oncology
Rui Jin, Ling Peng, Jiawei Shou, Jin Wang, Yin Jin, Fei Liang, Jing Zhao, Mengmeng Wu, Qin Li, Bin Zhang, Xiaoying Wu, Fen Lan, Lixia Xia, Junrong Yan, Yang Shao, Justin Stebbing, Huahao Shen, Wen Li, Yang Xia
Summary: Patients with EGFR-mutant lung squamous cell carcinoma have shorter progression-free survival compared to those with EGFR-mutant lung adenocarcinoma, and their genomic profiles are associated with the efficacy of EGFR-TKIs.
FRONTIERS IN ONCOLOGY
(2021)
Article
Oncology
Kazuhiko Nakagawa, Ernest Nadal, Edward B. Garon, Makoto Nishio, Takashi Seto, Nobuyuki Yamamoto, Keunchil Park, Jin-Yuan Shih, Luis Paz-Ares, Bente Frimodt-Moller, Annamaria H. Zimmermann, Sameera Wijayawardana, Carla Visseren-Grul, Martin Reck
Summary: In patients with EGFR-mutated NSCLC, the combination treatment of erlotinib and ramucirumab (RAM+ERL) demonstrated significant clinical benefits for both ex19del and ex21L858R mutation types, with similar treatment outcomes and tolerability. Baseline TP53 co-mutation was associated with improved outcomes in both mutation subtypes.
CLINICAL CANCER RESEARCH
(2021)
Review
Oncology
Susan L. Feldt, Christine M. Bestvina
Summary: Targeted therapy against genetic abnormalities in non-small cell lung cancer that has spread has improved patient outcomes. However, resistance eventually develops, and this paper summarizes the research on changes in the MET gene that occur after EGFR-targeted therapy. Medications targeting MET and combination therapies targeting both EGFR and MET show promise for overcoming this resistance. Larger trials are ongoing to assess the potential benefit for patients.
Review
Oncology
Yun-Zhu Xi, Li Xie, Xiao-Wu Tan, Sai-Li Zeng
Summary: This case report highlights the importance of histological evolution as a source of acquired drug resistance, as a stage IV lung adenocarcinoma with EGFR mutations converted to squamous cell carcinoma due to long-term administration of EGFR-TKIs.
FRONTIERS IN ONCOLOGY
(2022)
Article
Oncology
Vito Longo, Annamaria Catino, Michele Montrone, Pamela Pizzutilo, Francesco Pesola, Ilaria Marech, Iolanda Capone, Arsela Prelaj, Domenico Galetta
Summary: Patients with non-small cell lung cancer and uncommon EGFR mutations exhibit high heterogeneity, with some uncommon mutations showing sensitivity to TKIs comparable to common mutations. Additionally, compound EGFR mutations may be associated with a favorable prognosis. However, the rarity of complex EGFR mutations presents challenges in clinical decision-making.
Article
Pharmacology & Pharmacy
Yidong Feng, Yiting Lv, Xiaoqi Zhang, Kodithuwakku Nandani Darshika, Hanmin Huang, Hanlin Feng, Zhongfeng Shi
Summary: Non-small cell lung cancer (NSCLC) has various subclasses based on specific kinase mutations, with the most common being epidermal growth factor receptor (EGFR) somatic mutation. The development of tyrosine kinase inhibitors (TKIs) has been promoted for targeted therapy in NSCLC with EGFR mutations. However, not all patients respond equally to recommended TKIs, leading to the development of novel compounds. NEP010, a modified version of the marketed drug afatinib, showed improved inhibitory effects on EGFR mutant tumors. Pharmacokinetic and tissue distribution tests indicated that NEP010 may have increased efficacy by improving tissue exposure and targeting the lung, the organ of interest in clinical practice. In conclusion, NEP010 could be a potential therapeutic option for NSCLC patients with EGFR mutation.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2023)