Article
Multidisciplinary Sciences
Nathan Farrokhian, Jeff Maltas, Mina Dinh, Arda Durmaz, Patrick Ellsworth, Masahiro Hitomi, Erin McClure, Andriy Marusyk, Artem Kaznatcheev, Jacob G. Scott
Summary: In this study, the frequency-dependent interactions between a gefitinib-resistant non-small cell lung cancer population and its sensitive ancestor were measured experimentally. The cost of resistance was found to be insufficient in predicting competitive exclusion, and frequency-dependent growth rate measurements were necessary. Simulations showed that ecological growth effects can influence the predicted extinction time.
Article
Critical Care Medicine
Shun Lu, Jianying Zhou, Hong Jian, Lin Wu, Ying Cheng, Yun Fan, Jian Fang, Gongyan Chen, Zhihong Zhang, Dongqing Lv, Liyan Jiang, Rong Wu, Xiangming Jin, Xiaodong Zhang, Junhong Zhang, Conghua Xie, Gengyun Sun, Dongning Huang, Jiuwei Cui, Renhua Guo, Zhigang Han, Zhendong Chen, Jin Liang, Wu Zhuang, Xingsheng Hu, Aimin Zang, Yi Zhang, Shundong Cang, Yuanbo Lan, Xi Chen, Laiyu Liu, Xingya Li, Jun Chen, Rui Ma, Yanzhen Guo, Ping Sun, Panwen Tian, Yueyin Pan, Zhe Liu, Peiguo Cao, Lieming Ding, Yang Wang, Xiaobin Yuan, Pengxiang Wu
Summary: This phase 3 trial compared the efficacy and safety of befotertinib with icotinib as a first-line treatment for patients with EGFR mutation-positive NSCLC. The study found that befotertinib demonstrated superior efficacy in terms of progression-free survival compared to icotinib, although it was associated with more frequent adverse events.
LANCET RESPIRATORY MEDICINE
(2023)
Article
Pharmacology & Pharmacy
Lin Cao, Weipeng Hong, Peiheng Cai, Chuncao Xu, Xupeng Bai, Zhongxiang Zhao, Min Huang, Jing Jin
Summary: Lung cancer is the leading cause of cancer-related deaths, with gefitinib being a first-line treatment facing challenges in resistance. Research found up-regulated TKT expression in lung cancer cells, with CTS enhancing the effect of gefitinib by inhibiting TKT, potentially serving as a new adjuvant therapy for advanced lung cancer.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2021)
Review
Medicine, General & Internal
Janette Greenhalgh, Angela Boland, Victoria Bates, Fabio Vecchio, Yenal Dundar, Marty Chaplin, John A. Green
Summary: EGFR mutation positive non-small cell lung cancer is more common in women and occurs at a younger age. Treatment with single-agent or combination EGFR therapies shows advantages in improving tumor response rate and prolonging progression-free survival compared to other cytotoxic chemotherapy agents.
COCHRANE DATABASE OF SYSTEMATIC REVIEWS
(2021)
Article
Oncology
Si-Liang Wei, Jing-Jing Ye, Li Sun, Lei Hu, Yuan-Yuan Wei, Da-Wei Zhang, Meng-Meng Xu, Guang-He Fei
Summary: This study identified a novel mechanism involving circKIF20B/miR-615-3p/MEF2A signaling axis in the progression of gefitinib resistance in NSCLC. Downregulation of circKIF20B promotes resistance to gefitinib, while upregulation restores sensitivity. Exosomal circKIF20B may serve as a potential therapeutic target and liquid biopsy candidate in gefitinib-resistant NSCLC.
CANCER CELL INTERNATIONAL
(2023)
Article
Pharmacology & Pharmacy
Rui Chen, Zijun Qian, Xin Xu, Congcong Zhang, Yongjie Niu, Zhixian Wang, Jianli Sun, Xiao Zhang, Yongchun Yu
Summary: miR-7 plays a significant role in gefitinib resistance mechanism, it can be transferred via exosomes to reverse resistance and is associated with survival outcomes.
PHARMACOLOGICAL RESEARCH
(2021)
Article
Medicine, Research & Experimental
Dan Yan, Justus M. Huelse, Dmitri Kireev, Zikang Tan, Luxiao Chen, Subir Goyal, Xiaodong Wang, Stephen Frye, Madhusmita Behera, Frank Schneider, Suresh S. Ramalingam, Taofeek Owonikoko, H. Shelton Earp, Deborah DeRyckere, Douglas K. Graham
Summary: Acquired resistance is inevitable in non-small cell lung cancers (NSCLCs) treated with osimertinib (OSI). Activation of MERTK is associated with OSI resistance and inhibition of MERTK kinase can resensitize resistant cells to OSI.
JOURNAL OF CLINICAL INVESTIGATION
(2022)
Article
Oncology
Wenjuan He, Mingyang Qin, Yue Cai, Xiujuan Gao, Sisi Cao, Zhuo Wang, Hui Chen, Rong Xu
Summary: The study revealed that HOXC6 is highly expressed in Gef-resistant NSCLC cells and it plays a crucial role in Gef resistance by regulating multiple cellular functions. miR-27a can alleviate Gef resistance by inhibiting HOXC6 expression in NSCLC cells. High levels of HOXC6 and low levels of miR-27a are associated with more malignant clinical features and poorer survival in NSCLC patients.
AMERICAN JOURNAL OF CANCER RESEARCH
(2021)
Article
Pharmacology & Pharmacy
Bingjie Fu, Xiaojing Dou, Miao Zou, Hao Lu, Kaixuan Wang, Qingxia Liu, Yao Liu, Wei Wang, Meihua Jin, Dexin Kong
Summary: Amlodipine can suppress lung cancer cell proliferation by modulating multiple signaling pathways and protein expression, and it shows a good therapeutic effect when used alone or in combination with gefitinib.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Pharmacology & Pharmacy
Jinling Cui, Shuang Zhao, Hui Chen, Yuhan Fu, Kai Han, Shutao Yin, Chong Zhao, Lihong Fan, Hongbo Hu
Summary: Acquired resistance to EGFR TKI therapy compromises its efficacy in NSCLC. MET activation is a key strategy for cancer cells to acquire a refractory phenotype. The dysregulated amino acid metabolisms, including elevated expression of ASCT2, SLC7A11, and ASNS, contribute to the survival advantage of gefitinib-resistant cells. MSeA effectively suppresses tumor growth and inactivates the MET-TOPK signaling axis in gefitinib-resistant NSCLC.
BIOCHEMICAL PHARMACOLOGY
(2023)
Article
Medicine, General & Internal
Adrianus Johannes de Langen, Melissa L. Johnson, Julien Mazieres, Anne -Marie C. Dingemans, Giannis Mountzios, Miklos Pless, Jurgen Wolf, Martin Schuler, Herve Lena, Ferdinandos Skoulidis, Yasuto Yoneshima, Sang-We Kim, Helena Linardou, Silvia Novello, Anthonie J. van der Wekken, Yuanbin Chen, Solange Peters, Enriqueta Felip, Benjamin J. Solomon, Suresh S. Ramalingam, Christophe Dooms, Colin R. Lindsay, Carlos Gil Ferreira, Normand Blais, Cynthia C. Obiozor, Yang Wang, Bhakti Mehta, Tracy Varrieur, Gataree Ngarmchamnanrith, Bjorn Stollenwerk, David Waterhouse, Luis Paz-Ares
Summary: This study compared the efficacy and safety of Sotorasib with standard-of-care treatment in patients with non-small-cell lung cancer (NSCLC) with the KRASG12C mutation. The results showed that compared to docetaxel, Sotorasib significantly increased progression-free survival and had a more favorable safety profile.
Article
Multidisciplinary Sciences
Ming-Hung Chang, Kuo-Hwa Chiang, Jiunn-Min Shieh, Kuo-Chen Cheng, Chung-Han Ho
Summary: Miliary lung metastasis is not a dominant indicator for outcome evaluation in patients with non-small cell lung cancer harboring EGFR mutation under TKI prescription. Other strong prognostic indicators include performance status, liver metastasis, EGFR type, and generation of TKI.
SCIENTIFIC REPORTS
(2022)
Article
Multidisciplinary Sciences
Humna Hasan, Ikjot Singh Sohal, Zulaida Soto-Vargas, Anjali M. Byappanhalli, Sean E. Humphrey, Hana Kubo, Sarunya Kitdumrongthum, Sarah Copeland, Feng Tian, Arthit Chairoungdua, Andrea L. Kasinski
Summary: Extracellular vesicles (EVs) released from non-small cell lung cancer (NSCLC) cells play a crucial role in promoting cancer progression. There are differences in the secretion profile and the ability to induce phenotypic changes in non-tumorigenic cells among EVs derived from different NSCLC cell lines. EV-encapsulated RNA (EV-RNA) is identified as a key factor in mediating these phenotypes. The aggressiveness of NSCLC subtypes may be correlated with the ability of their respective EVs to induce cancerous phenotypes.
SCIENTIFIC REPORTS
(2022)
Article
Medicine, Research & Experimental
Zhongxing Bing, Jiashu Han, Zhibo Zheng, Naixin Liang
Summary: The research identified the regulation of the CASC9/miR-195-5p/FOXO3 positive feedback loop in NSCLC gefitinib resistance, which may help researchers develop potential therapeutic targets for NSCLC.
Article
Multidisciplinary Sciences
Dongliang Bian, Liangdong Sun, Junjie Hu, Liang Duan, Haoran Xia, Xinsheng Zhu, Fenghuan Sun, Lele Zhang, Huansha Yu, Yicheng Xiong, Zhida Huang, Deping Zhao, Nan Song, Jie Yang, Xiao Bao, Wei Wu, Jie Huang, Wenxin He, Yuming Zhu, Gening Jiang, Peng Zhang
Summary: This study aimed to assess the feasibility of neoadjuvant Afatinib treatment for stage III NSCLC patients. The results showed that Afatinib improved the objective response rate (ORR) in NSCLC patients and caused dynamic changes in the tumor microenvironment.
NATURE COMMUNICATIONS
(2023)
Article
Oncology
Hong-xia Tian, Zhi-hong Chen, Guang-Ling Jie, Zhen Wang, Hong-hong Yan, Si-pei Wu, Shui-lian Zhang, Dan-xia Lu, Xu-chao Zhang, Yi-long Wu
Summary: This study investigated the characteristics and prognostic features of the NF1 gene in EGFR mutant lung cancer patients. The results showed that NF1 mutations were enriched in older, male, and smoking patients, and were mutually exclusive with TP53, BRAF, and RASA1 mutations. TP53 mutation worsened the prognosis in cases of NF1 mutant or EGFR/NF1 co-mutant lung adenocarcinomas. NF1 mutations were not associated with overall survival in lung adenocarcinoma patients, but NF1/EGFR co-mutation patients had a longer overall survival than those with a single mutation of either gene. Furthermore, NF1 mutations significantly prolonged overall survival in EGFR mutant/TP53 wild-type patients but not in patients with EGFR/TP53 co-mutations.
Article
Oncology
Gilberto de Castro Jr, Iveta Kudaba, Yi-Long Wu, Gilberto Lopes, Dariusz M. Kowalski, Hande Z. Turna, Christian Caglevic, Li Zhang, Boguslawa Karaszewska, Konstantin K. Laktionov, Vichien Srimuninnimit, Igor Bondarenko, Kaoru Kubota, Rinee Mukherjee, Jianxin Lin, Fabricio Souza, Tony S. K. Mok, Byoung Chul Cho
Summary: This study presented the 5-year results of the KEYNOTE-042 trial, which showed that pembrolizumab demonstrated long-term clinical benefit compared to chemotherapy in patients with PD-L1-positive, locally advanced/metastatic non-small-cell lung cancer. Regardless of the level of PD-L1 expression, pembrolizumab had a better overall survival rate, confirming its status as a standard of care for this patient population.
JOURNAL OF CLINICAL 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.
Article
Oncology
Guang-Ling Jie, Lun-Xi Peng, Mei-Mei Zheng, Hao Sun, Song-Rong Wang, Si-Yang Maggie Liu, Kai Yin, Zhi-Hong Chen, Hong-Xia Tian, Jin-Ji Yang, Xu-Chao Zhang, Hai-Yan Tu, Qing Zhou, Catherine C. L. Wong, Yi-Long Wu
Summary: This study explores the clinical utility of plasma proteomics-derived biomarkers for MET-dysregulated NSCLC patients treated with MET inhibitors. Mass spectrometry analysis of longitudinal plasma samples revealed that the peripheral plasma proteomic characteristics were associated with treatment outcomes. A four-protein signature (MYH9, GNB1, ALOX12B, and HSD17B4) was identified as a high-accuracy predictor of response and progression-free survival in patients treated with MET inhibitors.
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)
Letter
Oncology
Ling Peng, Yawen Bin, Peng Ding, Lingjuan Chen, Hao Zeng, Zelong Xu, Liyan Ji, Xuan Gao, Pian Liu, Ye Wang, Sheng Zhang, Zhongxing Liao, Xuefeng Xia, Ruiguang Zhang, Fan Tong, Xiaorong Dong
CANCER COMMUNICATIONS
(2023)
Letter
Oncology
Si-Yang Maggie Liu, Cunte Chen, Yi-Kai Zhang, Wen-Zhao Zhong, Yi-Long Wu, Si-Yang Liu, Yangqiu Li
Summary: This study identified specific TCR sequences that can predict prognosis and favorable outcomes in EGFR-mutant NSCLC patients treated with adjuvant EGFR-TKI.
BIOMARKER RESEARCH
(2023)
Article
Oncology
Jhanelle E. Gray, Myung-Ju Ahn, Geoffrey R. Oxnard, Frances A. Shepherd, Fumio Imamura, Ying Cheng, Isamu Okamoto, Byoung Chul Cho, Meng-Chih Lin, Yi-Long Wu, Margarita Majem, Oliver Gautschi, Michael Boyer, Krishna C. Bulusu, Aleksandra Markovets, J. Carl Barrett, Rachel Hodge, Astrid Mckeown, Ryan J. Hartmaier, Juliann Chmielecki, Vassiliki A. Papadimitrakopoulou, Suresh S. Ramalingam
Summary: Plasma EGFRm analysis can predict the efficacy in EGFRm advanced NSCLC, especially when performed at around 3 weeks of treatment to predict the progression-free survival.
CLINICAL CANCER RESEARCH
(2023)
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)
Review
Oncology
Yang-Si Li, Guang-Ling Jie, Yi-Long Wu
Summary: Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are the standard treatment for non-small-cell lung cancer (NSCLC) with active EGFR mutations. However, resistance to EGFR-TKIs eventually develops, necessitating alternative treatment options for extensively pretreated patients with EGFR-mutant NSCLC. New agents, such as fourth-generation EGFR-TKIs, combination therapy with targeted drugs, and antibody-drug conjugates, have shown promising efficacy in clinical trials for this patient population. This review summarizes the current efforts in managing extensively pretreated patients with EGFR-mutant NSCLC.
THERAPEUTIC ADVANCES IN MEDICAL ONCOLOGY
(2023)
Article
Medicine, Research & Experimental
Muwen Yang, Yue Li, Lingzhi Kong, Shumei Huang, Lixin He, Pian Liu, Shuang Mo, Xiuqing Lu, Xi Lin, Yunyun Xiao, Dongni Shi, Xinjian Huang, Boyu Chen, Xiangfu Chen, Ying Ouyang, Jun Li, Chuyong Lin, Libing Song
Summary: HER2-targeted therapy is the main treatment for HER2+ breast cancer, but HER2 shedding reduces the effectiveness of anti-HER2 therapy. This study found that upregulation of DPAGT1 sustains HER2 shedding and confers trastuzumab resistance. Inhibition of DPAGT1 in combination with trastuzumab treatment can block HER2 signaling and reverse resistance.
JOURNAL OF CLINICAL INVESTIGATION
(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)
Letter
Oncology
Roy S. Herbst, Yi-Long Wu, Masahiro Tsuboi
JOURNAL OF CLINICAL ONCOLOGY
(2023)