Article
Biochemistry & Molecular Biology
Zi-Wei Chen, Gigin Lin, Hsuan-Jen Shih, Chiao-En Wu
Summary: This article reports a case of a patient with non-small cell lung cancer with EGFR gene mutations who responded well to brigatinib monotherapy after intolerable adverse events from afatinib and osimertinib treatments. The patient had EGFR del19/T790M/cis-C797S mutations.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Medicinal
Hao Chen, Mengzhen Lai, Tao Zhang, Yuqing Chen, Linjiang Tong, Sujie Zhu, Yang Zhou, Xiaomei Ren, Jian Ding, Hua Xie, Xiaoyun Lu, Ke Ding
Summary: This study reports the development of a novel EGFRT790M/C797S inhibitor that effectively inhibits the proliferation of EGFR-mutated NSCLC cells, suggesting a potential clinical application.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Oncology
Robin Guo, Michael Offin, A. Rose Brannon, Jason Chang, Andrew Chow, Lukas Delasos, Jeffrey Girshman, Olivia Wilkins, Caroline G. McCarthy, Alex Makhnin, Christina Falcon, Kerry Scott, Yuan Tian, Fabiola Cecchi, Todd Hembrough, Deepu Alex, Ronglai Shen, Ryma Benayed, Bob T. Li, Charles M. Rudin, Mark G. Kris, Maria E. Arcila, Natasha Rekhtman, Paul Paik, Ahmet Zehir, Alexander Drilon
Summary: In MET exon 14-altered lung cancers treated with a MET TKI, the genomic mechanisms of primary resistance remain unknown, while MET expression is correlated with treatment benefit.
CLINICAL CANCER RESEARCH
(2021)
Review
Pharmacology & Pharmacy
Matt Shirley, Susan J. Keam
Summary: Aumolertinib, a new-generation EGFR-TKI, shows promising efficacy and tolerability for both first-line and second-line treatment of advanced EGFR mutation-positive NSCLC, according to clinical trials conducted in China.
Article
Chemistry, Medicinal
M. Raymond Finlay, Peter Barton, Sue Bickerton, Michal Bista, Nicola Colclough, Darren A. E. Cross, Laura Evans, Nicolas Floc'h, Clare Gregson, Carine M. Guerot, David Hargreaves, Xiaoming Kang, Eva M. Lenz, Xu Li, Yi Liu, Olivier Lorthioir, Matthew J. Martin, Darren McKerrecher, Claire McWhirter, Daniel O'Neill, Jonathan P. Orme, Arash Mosallanejad, Amar Rahi, Paul D. Smith, Verity Talbot, Richard A. Ward, Gail Wrigley, Marta Wylot, Lin Xue, Tieguang Yao, Yang Ye, Xiliang Zhao
Summary: The research focused on the medicinal chemistry optimization of a biochemically potent but modestly cell-active, reversible EGFR inhibitor with sub-optimal physicochemical properties, leading to the discovery of compound 12 with improved cell potency, oral exposure, and in vivo activity in clinically relevant EGFR-mutant-driven disease models.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
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
Multidisciplinary Sciences
Tyler S. Beyett, Ciric To, David E. Heppner, Jaimin K. Rana, Anna M. Schmoker, Jaebong Jang, Dries J. H. De Clercq, Gabriel Gomez, David A. Scott, Nathanael S. Gray, Pasi A. Janne, Michael J. Eck
Summary: This study investigates the molecular mechanisms and structural basis of drug resistance in lung cancer and the combination of allosteric and ATP-competitive inhibitors to overcome resistance. The findings highlight the importance of the P-loop in the synergy between allosteric inhibitors and EGFR variants.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Kamrine E. Poels, Adam J. Schoenfeld, Alex Makhnin, Yosef Tobi, Yuli Wang, Heidie Frisco-Cabanos, Shaon Chakrabarti, Manli Shi, Chelsi Napoli, Thomas O. McDonald, Weiwei Tan, Aaron Hata, Scott L. Weinrich, Helena A. Yu, Franziska Michor
Summary: In this study, a computational model was used to identify an optimal dosing schedule for combination therapy of osimertinib and dacomitinib, which was confirmed tolerable and effective in an ongoing phase I clinical trial.
NATURE COMMUNICATIONS
(2021)
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
James Chih-Hsin Yang, Yuichiro Ohe, Chao -Hua Chiu, Xiaoling Ou, Mireille Cantarini, Pasi A. Janne, Ryan J. Hartmaier, Myung Ju Ahn
Summary: The combination of osimertinib and selumetinib showed promising antitumor activity and tolerability in patients with MET-negative, EGFRm advanced NSCLC who had progressed on previous EGFR-TKI treatment.
CLINICAL CANCER RESEARCH
(2022)
Article
Chemistry, Medicinal
Muammar Fawwaz, Kenji Mishiro, Ryuichi Nishii, Akira Makino, Yasushi Kiyono, Kazuhiro Shiba, Seigo Kinuya, Kazuma Ogawa
Summary: The study aimed to develop a PET imaging probe for detecting EGFR L858R/T790M mutations, and [Br-77]BrCO1686 showed high cytotoxicity and significant accumulation in tumor cells, indicating potential as a molecular probe for targeted imaging.
Article
Pharmacology & Pharmacy
Geunho Choi, Daegeun Kim, Junehwan Oh
Summary: This study utilized artificial intelligence to discover potential drugs that can overcome acquired resistance in lung cancer patients, reducing the limitations of the current drug discovery process.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Multidisciplinary Sciences
Hyoung-oh Jeong, Hayoon Lee, Hyemin Kim, Jinho Jang, Seunghoon Kim, Taejoo Hwang, David Whee-Young Choi, Hong Sook Kim, Naeun Lee, Yoo Mi Lee, Sehhoon Park, Hyun Ae Jung, Jong-Mu Sun, Jin Seok Ahn, Myung-Ju Ahn, Keunchil Park, Semin Lee, Se-Hoon Lee
Summary: The study found that specific cell types such as lung epithelial precursor cells and transitional effector T cells, as well as an immunosuppressive microenvironment, were enriched in the MPE of EGFR TKI-resistant patients, potentially associated with their response to TKI therapy.
Article
Biotechnology & Applied Microbiology
Xuehui Zhang, Chaoyuan Huang, Biyu Cui, Yebin Pang, Rong Liang, Xiaoling Luo
Summary: The combination of afatinib with ethacrynic acid showed strong synergistic antitumor effects in EGFR L858R/T790M-mutated NSCLC cells by inhibiting the activation of the WNT/beta-catenin pathway and suppressing the secretion of anti-inflammatory factors, providing a new therapeutic approach and potential for developing new drugs or optimizing afatinib dosage in clinical use for future antitumor therapy.
Article
Biochemistry & Molecular Biology
Milena Casula, Marina Pisano, Panagiotis Paliogiannis, Maria Colombino, Maria Cristina Sini, Angelo Zinellu, Davide Santeufemia, Antonella Manca, Stefania Casula, Silvia Tore, Renato Lobrano, Antonio Cossu, Giuseppe Palmieri
Summary: Oncogenic mutations in the EGFR gene are targets of tyrosine kinase inhibitors in lung adenocarcinoma patients. Liquid biopsy of ctDNA is increasingly used to detect EGFR mutations. This study compared three different techniques and found that real-time PCR-based methods showed equivalent detection ability to the NGS assay for circulating EGFR mutations, but the NGS assay had a poor ability to detect T790M.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Radiology, Nuclear Medicine & Medical Imaging
Alfredo Tartarone, Rosa Lerose, Michele Aieta
SEMINARS IN NUCLEAR MEDICINE
(2016)
Article
Oncology
Elena Verzoni, Ugo De Giorgi, Lisa Derosa, Orazio Caffo, Francesco Boccardo, Gaetano Facchini, Luca Porcu, Fabio De Vincenzo, Alberto Zaniboni, Vincenzo Emanuele Chiuri, Lucia Fratino, Daniele Santini, Vincenzo Adamo, Rocco De Vivo, Angelo Dinota, Caterina Messina, Riccardo Ricotta, Claudia Caserta, Claudio Scavelli, Marina Susi, Alfredo Tartarone, Giuseppe Surace, Alessandra Mosca, Michele Bruno, Sandro Barni, Paolo Grassi, Giuseppe Procopio
Article
Oncology
Alfredo Tartarone, Elisabetta Rossi, Rosa Lerose, Giuseppina Mambella, Giuseppe Calderone, Rita Zamarchi, Michele Aieta
Review
Oncology
Alfredo Tartarone, Pasqualina Giordano, Rosa Lerose, Maria Grazia Rodriquenz, Raffaele Conca, Michele Aieta
Editorial Material
Respiratory System
Alfredo Tartarone
JOURNAL OF THORACIC DISEASE
(2017)
Review
Respiratory System
Alfredo Tartarone, Rosa Lerose, Maria Grazia Rodriquenz, Giuseppina Mambella, Giuseppe Calderoni, Giovanni Bozza, Michele Aieta
JOURNAL OF THORACIC DISEASE
(2017)
Article
Respiratory System
Mariangela Manicone, Maria Chiara Scaini, Maria Grazia Rodriquenz, Antonella Facchinetti, Alfredo Tartarone, Michele Aieta, Rita Zamarchi, Elisabetta Rossi
JOURNAL OF THORACIC DISEASE
(2017)
Review
Oncology
Alfredo Tartarone, Rosa Lerose, Michele Aieta
Review
Oncology
Alfredo Tartarone, Giandomenico Roviello, Rosa Lerose, Raheleh Roudi, Michele Aieta, Pietro Zoppoli
Article
Nursing
Massimo Cirillo, Luciano Carlucci, Lorenzo Legramandi, Editta Baldini, Cosimo Sacco, Vittorina Zagonel, Silvana Leo, Francesca Di Fabio, Giuseppe Tonini, Maria Luisa Meacci, Alfredo Tartarone, Daniele Farci, Giampaolo Tortora, Marta Zaninelli, Vanna Maria Valori, Saverio Cinieri, Francesco Carrozza, Enrico Barbato, Valentina Fabbroni, Elisabetta Cretella, Teresa Gamucci, Gianluigi Lunardi, Sonia Zamboni, Giovanni Micallo, Stefano Cascinu, Carmine Pinto, Stefania Gori
JOURNAL OF CLINICAL NURSING
(2020)