Article
Multidisciplinary Sciences
Hui Deng, Qian Lei, Chengdi Wang, Zhoufeng Wang, Hai Chen, Gang Wang, Na Yang, Dan Huang, Quanwei Yu, Mengling Yao, Xue Xiao, Guonian Zhu, Cheng Cheng, Yangqian Li, Feng Li, Panwen Tian, Weimin Li
Summary: In this study, the authors present a fluorescence-activated cell sorting assay to identify activating EGFR mutations in lung cancer patients and demonstrate its utility in predicting response to EGFR-tyrosine kinase inhibitors.
NATURE COMMUNICATIONS
(2022)
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
Cell Biology
Carolien Eggermont, Philippe Giron, Maxim Noeparast, Hugo Vandenplas, Pedro Aza-Blanc, Gustavo J. Gutierrez, Jacques De Greve
Summary: In this study, a high-throughput siRNA kinome screen was performed to identify targets involved in functional drug tolerance against EGFR TKI in NSCLC. STYK1 was identified as a potential target that, when downregulated, enhances the effects of EGFR inhibition. The study also found that STYK1 selectively interacts with mutant EGFR and that its downregulation counteracts the upregulation of FGF1 induced by EGFR TKI. Co-targeting EGFR and STYK1 could lead to a better overall outcome for NSCLC patients.
CELL DEATH & DISEASE
(2022)
Review
Pharmacology & Pharmacy
Carmelo Laface, Felicia Maria Maselli, Anna Natalizia Santoro, Maria Laura Iaia, Francesca Ambrogio, Marigia Laterza, Chiara Guarini, Pierluigi De Santis, Martina Perrone, Palma Fedele
Summary: Approximately 17% of Western patients with NSCLC have activating EGFR gene mutations. Del19 and L858R are the most common mutations and positive predictive factors for EGFR TKIs. Osimertinib, a third-generation TKI, is currently the standard first-line therapy for advanced NSCLC patients with common EGFR mutations. However, resistance to TKIs remains a major challenge, and there is a need for further research to discover new genetic targets and develop new-generation drugs to overcome resistance.
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)
Article
Multidisciplinary Sciences
Shen Zhao, Wu Zhuang, Baohui Han, Zhengbo Song, Wei Guo, Feng Luo, Lin Wu, Yi Hu, Huijuan Wang, Xiaorong Dong, Da Jiang, Mingxia Wang, Liyun Miao, Qian Wang, Junping Zhang, Zhenming Fu, Yihua Huang, Chunwei Xu, Longyu Hu, Lei Li, Rong Hu, Yang Yang, Mengke Li, Xiugao Yang, Li Zhang, Yan Huang, Wenfeng Fang
Summary: This study reports the safety and preliminary efficacy of a phase I clinical trial (JMT101) combining an anti-EGFR antibody with EGFR-TKI in patients with non-small cell lung cancer (NSCLC) harboring EGFR exon 20 insertions. The combination therapy demonstrated good tolerability and promising efficacy in patients.
NATURE COMMUNICATIONS
(2023)
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)
Review
Oncology
Karan Seegobin, Umair Majeed, Nathaniel Wiest, Rami Manochakian, Yanyan Lou, Yujie Zhao
Summary: ICI therapy in NSCLC shows promising outcomes in certain cases with actionable mutations, but its efficacy remains unclear in other cases. The correlation between PD-L1 expression or tumor mutation burden and treatment outcome is inconclusive.
FRONTIERS IN ONCOLOGY
(2021)
Article
Multidisciplinary Sciences
Anna Gogleva, Dimitris Polychronopoulos, Matthias Pfeifer, Vladimir Poroshin, Michael Ughetto, Matthew J. Martin, Hannah Thorpe, Aurelie Bornot, Paul D. Smith, Ben Sidders, Jonathan R. Dry, Miika Ahdesmaki, Ultan McDermott, Eliseo Papa, Krishna C. Bulusu
Summary: Resistance to EGFR inhibitors is a major challenge in the treatment of non-small cell lung cancer. The authors developed a recommender system that ranks genes based on diverse types of evidence, identifying potential mechanisms of EGFR inhibitor resistance.
NATURE COMMUNICATIONS
(2022)
Review
Biochemistry & Molecular Biology
Mohammad Mojtaba Sadeghi, Mohamed F. Salama, Yusuf A. Hannun
Summary: Driver-directed therapeutics have significantly improved cancer treatment efficacy and quality of life, but resistance acquisition remains a major challenge in targeted therapy for NSCLC. PKC isoforms have been implicated as mediators of drug resistance in NSCLC, with upregulation correlating with worse prognosis. Predictive biomarkers for PKC activity are needed for better results in clinical trials, and tandem inhibition of PKC and molecular drivers may offer a potential therapeutic strategy to prevent resistance emergence.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Oncology
Elizabeth S. Duke, Liza Stapleford, Nicole Drezner, Anup K. Amatya, Pallavi S. Mishra-Kalyani, Yuan -Li Shen, Kimberly Maxfield, Jeanne Fourie Zirkelbach, Youwei Bi, Jiang Liu, Xinyuan Zhang, Hezhen Wang, Yuching Yang, Nan Zheng, Kelie Reece, Emily Wearne, Jacqueline J. Glen, Idara Ojofeitimi, Barbara Scepura, Abhilasha Nair, Rama Kamesh Bikkavilli, Soma Ghosh, Reena Philip, Richard Pazdur, Julia A. Beaver, Harpeet Singh, Martha Donoghue
Summary: The FDA has granted accelerated approval for a new drug to treat adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with EGFR exon 20 insertion mutations. The approval was based on data from a clinical trial and the drug showed an overall response rate of 28% with a median duration of response of 17.5 months. Common adverse reactions include diarrhea, rash, nausea, stomatitis, vomiting, decreased appetite, paronychia, fatigue, dry skin, and musculoskeletal pain. This is the first oral targeted therapy approved for patients with advanced EGFR exon 20 insertion mutation-positive NSCLC.
CLINICAL CANCER RESEARCH
(2023)
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
Alex Martinez-Marti, Enriqueta Felip, Francesco Mattia Mancuso, Ginevra Caratu, Judit Matito, Paolo Nuciforo, Irene Sansano, Nely Diaz-Mejia, Susana Cedres, Ana Callejo, Patricia Iranzo, Nuria Pardo, Josep Maria Miquel, Alejandro Navarro, Ana Vivancos, Miriam Sanso
Summary: The study analyzed tumor samples from 5 NSCLC patients, revealing homogeneity in pathogenic mutations and TKI resistance mechanisms in most patients. Despite different resistance mechanisms depending on the patient and treatment line, a single metastasis biopsy from EGFR-mutated NSCLC patients could provide valuable information under selective TKI pressure.
BRITISH JOURNAL OF CANCER
(2021)
Review
Oncology
Catherine B. Meador, Lecia Sequist, Zofia Piotrowska
Summary: EGFR ins20 mutations, occurring in approximately 10% of EGFR-activating mutations, have historically shown reduced sensitivity to early-generation EGFR TKIs. However, recent advancements in scientific understanding and clinical detection techniques have improved our ability to develop effective therapies for this subset of EGFR-mutant NSCLC.
Article
Biochemistry & Molecular Biology
Cathy E. Richards, Yasir Y. Elamin, Aoife Carr, Kathy Gately, Shereen Rafee, Mattia Cremona, Emer Hanrahan, Robert Smyth, Daniel Ryan, Ross K. Morgan, Susan Kennedy, Lance Hudson, Joanna Fay, Kenneth O'Byrne, Bryan T. Hennessy, Sinead Toomey
Summary: PTPN11 mutations are common in lung cancer and may serve as a therapeutic target. Mutant PTPN11 promotes the growth and transformation of lung cancer cells, and SHP2 inhibitor in combination with PI3K inhibitor can inhibit the activation of the MAPK pathway, thus inhibiting lung cancer development.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Chang-Mei Weng, Qing Li, Kui-Jun Chen, Cheng-Xiong Xu, Meng-Sheng Deng, Tao Li, Dong-Dong Zhang, Zhao-Xia Duan, Zhi-Qiang Chen, Guan-Hua Li, Jing Chen, Jian-Min Wang
BIOSCIENCE REPORTS
(2020)
Article
Oncology
Zhi-Wei Zhou, Chiara Ambrogio, Asim K. Bera, Qing Li, Xing-Xiao Li, Lianbo Li, Jieun Son, Sudershan Gondi, Jiaqi Li, Emily Campbell, Hua Jin, Jeffrey J. Okoro, Cheng-Xiong Xu, Pasi A. Janne, Kenneth D. Westover
Article
Multidisciplinary Sciences
Jessie Huang, Hong Lam, Cynthia Koziol-White, Nathachit Limjunyawong, Donghwa Kim, Nicholas Kim, Nikhil Karmacharya, Premraj Rajkumar, Danielle Firer, Nicholas M. Dalesio, Joseph Jude, Richard C. Kurten, Jennifer L. Pluznick, Deepak A. Deshpande, Raymond B. Penn, Stephen B. Liggett, Reynold A. Panettieri, Xinzhong Dong, Steven S. An
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2020)
Article
Biochemistry & Molecular Biology
Donghwa Kim, Maria Castano, Lauren K. Lujan, Jung A. Woo, Stephen B. Liggett
Summary: The functional desensitization of bitter taste receptor TAS2R14 occurs through GRK phosphorylation of CT residues and beta-arrestin binding. Additionally, beta-arrestin's role in the internalization and trafficking of the receptor also requires GRK phosphorylation of IL3 residues.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Oncology
Qing Li, Zhi-Wei Zhou, Wei Duan, Cheng-Yuan Qian, Shu-Nan Wang, Meng-Sheng Deng, Dan Zi, Jian-Min Wang, Cheng-Yi Mao, Guanbin Song, Dong Wang, Kenneth D. Westover, Cheng-Xiong Xu
Summary: High APE1 expression is associated with lymph node metastasis in cervical cancer and linked to epithelial to mesenchymal transition (EMT). APE1 promotes invasion and metastasis of cervical cancer cells, while inhibiting APE1 may suppress EMT. Targeting APE1 redox function could be a novel strategy for inhibiting cervical cancer metastasis.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2021)
Article
Chemistry, Physical
Moon Young Yang, Soo-Kyung Kim, Donghwa Kim, Stephen B. Liggett, William A. Goddard
Summary: The study identified the activation structure of TAS2R5 receptors and the binding mode with agonists, providing valuable insights into how agonists activate TAS2R5 and the design of novel drugs.
JOURNAL OF PHYSICAL CHEMISTRY LETTERS
(2021)
Article
Multidisciplinary Sciences
Donghwa Kim, Alina Tokmakova, Lauren K. Lujan, Hannah R. Strzelinski, Nicholas Kim, Maliheh Najari Beidokhti, Marc A. Giulianotti, Amirhossein Mafi, Jung-A A. Woo, Steven S. An, William A. Goddard, Stephen B. Liggett
Summary: The study identified a potentially beneficial β(2)-adrenergic receptor agonist, C1-S, for treating asthma, which diverges from the influence of β-arrestin by retaining Gas signaling, resulting in biologically relevant biasing effects.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Review
Oncology
Hao Luo, Jinlu Shan, Hong Zhang, Guanbin Song, Qing Li, Cheng-Xiong Xu
Summary: Dysregulation of epigenetic processes plays a crucial role in promoting small cell lung cancer (SCLC), and it also affects tumor immunogenicity and immune cell functions. Current clinical trials have shown that epigenetics-targeting drugs may enhance antitumor immune response, indicating the potential of combining epigenetic agents with immunotherapy as a therapeutic approach for SCLC.
SEMINARS IN CANCER BIOLOGY
(2022)
Article
Health Care Sciences & Services
Alina Tokmakova, Donghwa Kim, William A. Goddard, Stephen B. Liggett
Summary: Signals from G-protein-coupled receptors are frequently targeted in therapeutics. Biased agonists that favor Gs coupling over β-arrestin binding could provide personalized therapy for obstructive lung diseases.
JOURNAL OF PERSONALIZED MEDICINE
(2022)
Review
Genetics & Heredity
Donghwa Kim, Alina Tokmakova, Jung-A A. Woo, Steven S. An, William A. Goddard, Stephen B. Liggett
Summary: GPCRs are a superfamily of receptors activated by a variety of ligands, able to activate different signaling pathways with varying therapeutic effects. Biased ligands may offer new opportunities for drug development by selectively targeting specific pathways, though challenges in understanding structure-function relationships need to be addressed.
MOLECULAR DIAGNOSIS & THERAPY
(2022)
Article
Biochemistry & Molecular Biology
Jung-A A. Woo, Maria Castano, Teresa R. Kee, Jordan Lee, Cynthia J. Koziol-White, Steven S. An, Donghwa Kim, David E. Kang, Stephen B. Liggett
Summary: TAS2Rs are bitter taste receptors expressed on human airway smooth muscle (HASM) cells. Activation of TAS2Rs promotes airway relaxation through severing of F-actin. This destabilization of actin is due to cofilin dephosphorylation, which is mediated by TAS2R-induced deactivation of LIM domain kinase. The understanding of this mechanism provides new insights into potential targets for bronchodilators.
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
(2023)
Meeting Abstract
Allergy
Juan Carlos Cardet, Donghwa Kim, Eugene Bleecker, Thomas Casale, Elliot Israel, David Mauger, Deborah Meyers, Yaping Tu, Stephen Liggett, Victor Ortega
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
(2022)
Article
Chemistry, Medicinal
Donghwa Kim, Steven S. An, Hong Lam, James W. Leahy, Stephen B. Liggett
ACS PHARMACOLOGY & TRANSLATIONAL SCIENCE
(2020)
Article
Oncology
Junfeng Guo, Shuzuo Zhou, Ping Huang, Shuai Xu, Gang Zhang, Haitao He, Yi Zeng, Cheng-Xiong Xu, Haesung Kim, Yinghui Tan
AMERICAN JOURNAL OF CANCER RESEARCH
(2020)
Meeting Abstract
Oncology
Zhiwei Zhou, Chiara Ambrogio, Asim Bera, Li Qing, Xu Cheng-Xiong, Pasi Janne, Ken Westover
MOLECULAR CANCER RESEARCH
(2020)