Article
Biochemistry & Molecular Biology
Shiqi Ma, Lu Zhang, Yuan Ren, Wei Dai, Tingqing Chen, Liping Luo, Juan Zeng, Kun Mi, Jinyi Lang, Bangrong Cao
Summary: This study revealed the impact of EREG on EGFR-TKI sensitivity and its mechanisms in NSCLC, suggesting macrophage-produced EREG as a potential novel regulator and biomarker for EGFR-TKI therapy in NSCLC.
Article
Medicine, Research & Experimental
Suntae Kim, Jang Su Jeon, Yong June Choi, Ga Hee Baek, Sang Kyum Kim, Keon Wook Kang
Summary: The heterogeneity of glutamine metabolism in EGFR-TKI-resistant lung cancer cells was evaluated in this study. It was found that CB-839, a specific GLS inhibitor, can effectively inhibit glutamine metabolism and exert enhanced anti-proliferating effects on acquired EGFR-TKI-resistant lung cancer cells.
Review
Oncology
Jingwei Li, Peiyi Li, Jun Shao, Shufan Liang, Yuntian Wan, Qiran Zhang, Changshu Li, Yalun Li, Chengdi Wang
Summary: This review summarizes the potential mechanisms of noncoding RNAs in EGFR TKI-resistant lung cancer and their clinical applications, and highlights the barriers that need to be addressed.
Article
Chemistry, Multidisciplinary
Peijun Cao, Yongwen Li, Ruifeng Shi, Yin Yuan, Hao Gong, Guangsheng Zhu, Zihe Zhang, Chen Chen, Hongbing Zhang, Minghui Liu, Zhenhua Pan, Hongyu Liu, Jun Chen
Summary: Lung cancer has the highest mortality rate globally, and EGFR-TKIs have improved the survival of NSCLC patients by inducing autophagy. However, acquired resistance is common. Drug-resistant cells exhibit higher autophagy activity, and autophagy inhibitors can enhance the toxicity of EGFR-TKIs. Moreover, increased autophagy is associated with decreased EZH2 expression.
FRONTIERS IN CHEMISTRY
(2022)
Review
Cell Biology
Dylan A. Farnsworth, Yankuan T. Chen, Georgia de Rappard Yuswack, William W. Lockwood
Summary: Mutant EGFR is a molecular driver of non-small cell lung cancer, and tumors with these mutations often rely on sustained oncogene signaling. While inhibiting EGFR with tyrosine kinase inhibitors has shown clinical benefits, resistance remains a challenge. The genetic mechanisms underlying EGFR dependency and factors allowing tumor cells to escape this dependency are still not fully understood.
Article
Oncology
Fang Huang, Jian Cui, Jingxuan Wan, Xue Yuan, Yuanzhe Zhu, Xiangxiang Wu, Wei Zuo, Tiantian Zhao
Summary: SLC12A8 mediates TKI resistance in EGFR-mutant lung cancer through the PDK1/AKT axis.
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Tohru Ohmori, Toshimitsu Yamaoka, Koichi Ando, Sojiro Kusumoto, Yasunari Kishino, Ryou Manabe, Hironori Sagara
Summary: The tyrosine kinase activity of EGFR plays critical roles in cell proliferation, regeneration, tumorigenesis, and anticancer resistance. EGFR-TKI-induced ILD can be tolerable and manageable, but may also result in serious lung injury, particularly in the presence of specific risk factors.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Mark C. Howell Jr., Ryan Green, Junior Cianne, Guy W. Dayhoff II, Vladimir N. Uversky, Shyam Mohapatra, Subhra Mohapatra
Summary: EGFR signaling and mutations are crucial in cancer, especially in drug resistance. This study analyzed RNA sequencing and protein array data to identify key proteins that could be targeted to overcome EGFR TKI resistance in lung cancer.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(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)
Article
Oncology
Jiaye Lu, Jingwei Li, Ziyou Lin, Huaxuan Li, Linlin Lou, Wen Ding, Shumin Ouyang, Yonghui Wu, Yuanzhen Wen, Xiaobing Chen, Peibin Yue, Yuanxiang Wang, Peiqing Liu, Jinjian Lu, Jian Zhang, Weineng Feng, Xiaolei Zhang
Summary: This study revealed the role of tumor-associated macrophages (TAMs) in acquired drug resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in lung cancer. M2-like reprogramming of TAMs and reduced phagocytosis were observed in gefitinib-resistant lung cancer cells. CD47 upregulation in TKI-resistant cells enhanced M2 macrophage polarization and cancer cell escape from macrophage phagocytosis. Inhibition of STAT3 alleviated the acquired resistance to EGFR-TKIs by inhibiting the CD47-SIRP alpha signaling axis and M2 polarization.
Article
Oncology
Sze-Ching Wong, Chun-Chieh Yeh, Xun-Yu Zhang, Chih-Ying Hsieh, Chia-Chien Lo, Ting-Ting Kuo, Ching-Chan Lin, Chih-Hua Chao, Jing-Pei Liu, Ling-Chu Chang, Lu-Hai Wang, Yuh-Pyng Sher
Summary: CUB domain-containing protein 1 (CDCP1) contributes to EGFR TKI resistance in lung cancer, and this study identified a CDCP1 reducer called 8-isopentenylnaringenin (8PN) that synergistically improves TKI treatment. 8PN treatment reduced CDCP1 protein levels and malignant features, and in TKI-resistant lung cancer cells, the combination of 8PN and TKI had additive effects on cell death and reduced the downstream EGFR pathway signaling. Mechanistically, 8PN increased IL6 and IL8 expression, induced neutrophil infiltration, and enhanced neutrophil-mediated cytotoxicity. Combination therapy effectively reduced tumor growth and necrosis in vivo.
MOLECULAR ONCOLOGY
(2023)
Article
Pharmacology & Pharmacy
Yi Li, Qing-Long Yu, Tong-Fang Li, Ya-Ni Xiao, Li Zhang, Qiu-Yan Zhang, Chun-Guang Ren, Hong-Lei Xie
Summary: The study demonstrates that the newly developed drug XHL11 exhibits strong anti-tumor activity against H1975 cells with EGFRL858R/T790M mutation and shows potential for therapeutic use in NSCLC patients. Additional research is needed to further explore the effectiveness and tolerability of XHL11 as an EGFR TKI.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2021)
Article
Oncology
Jun-Feng Liu, Xu-Sheng Sun, Jin-Huan Yin, Xi-E Xu
Summary: This retrospective study aimed to address the effect of adjuvant chemotherapy before adjuvant EGFR-TKI therapy and the duration of EGFR-TKI therapy on survival outcomes in patients with NSCLC. The results showed that adjuvant EGFR-TKI treatment was effective for patients with stage II-IIIA EGFR-mutation positive NSCLC. Patients with stage I and pathological risk factors were also suitable for receiving adjuvant EGFR-TKI therapy.
FRONTIERS IN ONCOLOGY
(2023)
Article
Oncology
Wen-Jui Wu, Sheng-Hsiung Yang, Hsin-Pei Chung, Chia-Te Yen, Yen-Ting Chen, Wei-Chin Chang, Jian Su, Hsuan-Yu Chen
Summary: This study retrospectively analyzed the prevalence of EGFR Q787Q polymorphism and its impact on the efficacy of TKI treatment in patients with lung adenocarcinoma. The findings suggest that EGFR Q787Q polymorphism is common in patients with EGFR-mutated lung adenocarcinoma and serves as a protective predictor of overall survival.
FRONTIERS IN ONCOLOGY
(2022)
Review
Pharmacology & Pharmacy
Rashidi Dzul Keflee, Kok Hoong Leong, Satoshi Ogawa, Jerome Bignon, Mun Chiang Chan, Kin Weng Kong
Summary: This review provides an overview of the multifaceted mechanisms of resistance towards EGFR-TKIs, as well as the challenges and perspectives that should be addressed in strategising chemotherapeutic treatments to overcome the ever-evolving and adaptive nature of NSCLC.
BIOCHEMICAL PHARMACOLOGY
(2022)
Correction
Genetics & Heredity
Yuan Yuan, Young Seok Ju, Youngwook Kim, Jun Li, Yumeng Wang, Christopher J. Yoon, Yang Yang, Inigo Martincorena, Chad J. Creighton, John N. Weinstein, Yanxun Xu, Leng Han, Hyung-Lae Kim, Hidewaki Nakagawa, Keunchil Park, Peter J. Campbell, Han Liang
Correction
Genetics & Heredity
Yuan Yuan, Young Seok Ju, Youngwook Kim, Jun Li, Yumeng Wang, Christopher J. Yoon, Yang Yang, Inigo Martincorena, Chad J. Creighton, John N. Weinstein, Yanxun Xu, Leng Han, Hyung-Lae Kim, Hidewaki Nakagawa, Keunchil Park, Peter J. Campbell, Han Liang
Summary: A revised version of this paper has been published and can be accessed through a link at the top.
Article
Oncology
Gilberto de Castro Jr, Naiyer A. Rizvi, Peter Schmid, Konstantinos Syrigos, Claudio Martin, Nobuyuki Yamamoto, Ying Cheng, Vladimir Moiseyenko, Yvonne Summers, Ihor Vynnychenko, Sung Yong Lee, Maciej Bryl, Alona Zer, Mustafa Erman, Constanta Timcheva, Rajiv Raja, Kirsha Naicker, Urban Scheuring, Jill Walker, Helen Mann, Vikram Chand, Tony Mok
Summary: In the NEPTUNE study, first-line durvalumab plus tremelimumab did not show significant improvement in overall survival compared to chemotherapy in patients with metastatic NSCLC.
JOURNAL OF THORACIC ONCOLOGY
(2023)
Article
Oncology
Ryan J. Hartmaier, Aleksandra A. Markovets, Myung Ju Ahn, Lecia Sequist, Ji-Youn Han, Byoung Chul Cho, Helena A. Yu, Sang-We Kim, James Chih-Hsin Yang, Jong-Seok Lee, Wu-Chou Su, Dariusz M. Kowalski, Sergey Orlov, Song Ren, Paul Frewer, Xiaoling Ou, Darren A. E. Cross, Nisha Kurian, Mireille Cantarini, Pasi A. Jaenne
Summary: Combining MET inhibitor and EGFR tyrosine kinase inhibitor can overcome acquired osimertinib resistance mediated by MET. In this study, savolitinib and osimertinib combination therapy showed promising results in advanced non-small cell lung cancer patients with MET amplification and EGFR mutation who had progressed on prior EGFR-TKI treatment. The combination therapy demonstrated acceptable safety profile and improved antitumor activity.
Editorial Material
Oncology
Hyun Ae Jung, Jinyeong Lim, Yoon-La Choi, Jhingook Kim, Keunchil Park
CLINICAL CANCER RESEARCH
(2023)
Article
Oncology
Chong Kin Liam, Azura Rozila Ahmad, Te-Chun Hsia, Jianying Zhou, Dong-Wan Kim, Ross Andrew Soo, Ying Cheng, Shun Lu, Sang Won Shin, James Chih-Hsin Yang, Yiping Zhang, Jun Zhao, Karin Berghoff, Rolf Bruns, Andreas Johne, Yi-Long Wu
Summary: The final analysis of the INSIGHT phase II study showed that tepotinib plus gefitinib can improve progression-free survival (PFS) and overall survival (OS) compared to chemotherapy in a subgroup of patients with MET-amplified EGFR-mutant NSCLC after progression on EGFR inhibitors.
CLINICAL CANCER RESEARCH
(2023)
Review
Oncology
Benjamin P. Levy, Enriqueta Felip, Martin Reck, James C. H. Yang, Federico Cappuzzo, Yasuto Yoneshima, Caicun Zhou, Siddhartha Rawat, Jingdong Xie, Priyanka Basak, Lu Xu, Jacob Sands
Summary: The TROPION-Lung08 study is a Phase III trial evaluating the safety and efficacy of Dato-DXd plus pembrolizumab versus pembrolizumab monotherapy for advanced/metastatic NSCLC patients without AGAs and with PD-L1 tumor proportion score =50%. The primary endpoints are progression-free survival and overall survival, while secondary endpoints include objective response rate, duration of response, safety, and presence of antidrug antibodies.
Article
Oncology
Lecia V. Sequist, James Chih-Hsin Yang, Nobuyuki Yamamoto, Kenneth O'Byrne, Vera Hirsh, Tony Mok, Sarayut Lucien Geater, Sergey Orlov, Chun-Ming Tsai, Michael Boyer, Wu-Chou Su, Jaafar Bennouna, Terufumi Kato, Vera Gorbunova, Ki Hyeong Lee, Riyaz Shah, Dan Massey, Victoria Zazulina, Mehdi Shahidi, Martin Schuler
Summary: The study compared the efficacy of chemotherapy with afatinib in the treatment of EGFR-mutated lung adenocarcinoma. Results showed that afatinib prolonged progression-free survival and improved the quality of life for patients, when compared with chemotherapy.
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Article
Oncology
Lok Seng Chan, Johnson Liu, Molly S. C. Li, Lili Li, Qian Tao, Tony S. K. Mok
Summary: Selenite is found to induce both apoptosis and ferroptosis in lung cancer cells, especially those with EGFR and KRAS mutations. It activates the p38-ATF4-DDIT3 pathway for ferroptosis induction and influences DNA methylation machinery. Combining selenite with osimertinib or adagrasib enhances the therapeutic effect.
CLINICAL EPIGENETICS
(2023)
Review
Oncology
Joyce W. Y. Chan, Ivan C. H. Siu, Aliss T. C. Chang, Molly S. C. Li, Rainbow W. H. Lau, Tony S. K. Mok, Calvin S. H. Ng
Summary: Traditionally, treatment options for lung cancer include surgery, radiotherapy, and percutaneous ablation. However, with the development of new technologies such as electromagnetic navigation bronchoscopy and robotic bronchoscopy, transbronchial therapies are emerging as a viable option. This is particularly promising for high-risk patients and those who cannot undergo surgery. The demand for local ablation is also increasing due to a rising incidence of multiple synchronous lung cancers and the shift towards prevention rather than treatment.
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
Oncology
Byoung Chul Cho, Myung-Ju Ahn, Jin Hyoung Kang, Ross A. Soo, Thanyanan Reungwetwattana, James Chih-Hsin Yang, Irfan Cicin, Dong-Wan Kim, Yi-Long Wu, Shun Lu, Ki Hyeong Lee, Yong-Kek Pang, Anastasia Zimina, Chin Heng Fong, Elena Poddubskaya, Ahmet Sezer, Soon Hin How, Pongwut Danchaivijitr, Yukyung Kim, Yeji Lim, Taewon An, Hana Lee, Hae Mi Byun, Bojan Zaric
Summary: Lazertinib demonstrated significant efficacy improvement compared with gefitinib in the first-line treatment of EGFR-mutated advanced NSCLC, with a manageable safety profile. The results of this study are of great importance for improving patient outcomes and guiding clinical practice.
JOURNAL OF CLINICAL ONCOLOGY
(2023)