Article
Oncology
Boyeon Kim, Young Soo Park, Jae Sook Sung, Jong Won Lee, Saet Byeol Lee, Yeul Hong Kim
Summary: The study investigated the impact of clathrin-mediated EGFR endocytosis on the efficacy of gefitinib in wild-type EGFR NSCLC cells. The results showed that inhibiting clathrin-mediated endocytosis combined with gefitinib treatment decreased cell survival and induced apoptosis in gefitinib-refractory cell lines. The findings suggest that targeting clathrin-mediated EGFR endocytosis could be a potential option for the treatment of wild-type EGFR NSCLC.
Article
Oncology
K. Tamura, T. Yoshida, K. Masuda, Y. Matsumoto, Y. Shinno, Y. Okuma, Y. Goto, H. Horinouchi, N. Yamamoto, Y. Ohe
Summary: This retrospective study investigated the activity of EGFR-TKIs in untreated EGFR-mutated NSCLC patients with leptomeningeal metastases (LM). The results showed that osimertinib had better outcomes in LM compared to first-generation TKIs, especially in patients with exon 19 deletion.
Article
Oncology
Alexis B. Cortot, Anne Madroszyk, Etienne Giroux-Leprieur, Olivier Molinier, Elisabeth Quoix, Henri Berard, Josiane Otto, Isabelle Rault, Denis Moro-Sibilot, Judith Raimbourg, Elodie Amour, Franck Morin, Jose Hureaux, Lionel Moreau, Didier Debieuvre, Hugues Morel, Aldo Renault, Eric Pichon, Benjamin Huret, Sandrine Charpentier, Marc G. Denis, Jacques Cadranel
Summary: The addition of cetuximab to afatinib in the treatment of treatment-naive advanced EGFR-mutant NSCLC did not show any significant improvement in efficacy, suggesting that further investigation into this combination therapy may not be warranted.
CLINICAL CANCER RESEARCH
(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
Multidisciplinary Sciences
Mari Tone, Kota Iwahori, Takayuki Shiroyama, Shinji Futami, Yujiro Naito, Kiyoharu Fukushima, Kotaro Miyake, Shohei Koyama, Haruhiko Hirata, Izumi Nagatomo, Hisashi Wada, Yoshito Takeda, Atsushi Kumanogoh
Summary: Minocycline administration in NSCLC patients treated with first-line EGFR-TKIs was found to correlate with longer PFS and OS, independent of skin rash. This retrospective analysis suggests that minocycline may have a positive impact on the treatment outcomes of EGFR-mutant NSCLC patients.
SCIENTIFIC REPORTS
(2023)
Article
Engineering, Biomedical
Duo Wang, Jun Zhou, Weimin Fang, Cuiqing Huang, Zerong Chen, Meng Fan, Ming-Rong Zhang, Zeyu Xiao, Kuan Hu, Liangping Luo
Summary: In this study, a multifunctional superparamagnetic nanotheranostic agent was developed to enhance the efficacy of Erlotinib in EGFR-wt NSCLC. The nanoparticles co-delivered Erlotinib and a VEGF inhibitor (Bev) to EGFR-wt tumors, inhibiting tumor growth and promoting vascular normalization. The tumor engagement of nanoparticles and vascular normalization could be tracked by MRI.
BIOACTIVE MATERIALS
(2022)
Article
Multidisciplinary Sciences
Tzu-Hsuan Chiu, Pi-Hung Tung, Chi-Hsien Huang, Jia-Shiuan Ju, Allen Chung-Cheng Huang, Chin-Chou Wang, Ho-Wen Ko, Ping-Chih Hsu, Yueh-Fu Fang, Yi-Ke Guo, Chih-Hsi Scott Kuo, Cheng-Ta Yang
Summary: This study compared the efficacy of EGFR-TKI monotherapy and EGFR-TKI plus bevacizumab in real-world non-small cell lung cancer patients with EGFR mutation. The results showed that EGFR-TKI plus bevacizumab significantly improved overall survival and reduced the risk of death compared to EGFR-TKI monotherapy.
SCIENTIFIC REPORTS
(2022)
Article
Critical Care Medicine
Yosuke Kawashima, Tatsuro Fukuhara, Haruhiro Saito, Naoki Furuya, Kana Watanabe, Shunichi Sugawara, Shunichiro Iwasawa, Yoshio Tsunezuka, Ou Yamaguchi, Morihito Okada, Kozo Yoshimori, Ichiro Nakachi, Masahiro Seike, Koichi Azuma, Futoshi Kurimoto, Yukari Tsubata, Yuka Fujita, Hiromi Nagashima, Gyo Asai, Satoshi Watanabe, Masaki Miyazaki, Koichi Hagiwara, Toshihiro Nukiwa, Satoshi Morita, Kunihiko Kobayashi, Makoto Maemondo
Summary: The combination treatment of bevacizumab and erlotinib did not prolong overall survival in patients with metastatic EGFR-mutant NSCLC, but both treatment groups showed relatively long survival durations.
LANCET RESPIRATORY MEDICINE
(2022)
Article
Oncology
Ciric To, Tyler S. Beyett, Jaebong Jang, William W. Feng, Magda Bahcall, Heidi M. Haikala, Bo H. Shin, David E. Heppner, Jaimin K. Rana, Brittaney A. Leeper, Kara M. Soroko, Michael J. Poitras, Prafulla C. Gokhale, Yoshihisa Kobayashi, Kamal Wahid, Kari J. Kurppa, Thomas W. Gero, Michael D. Cameron, Atsuko Ogino, Mierzhati Mushajiang, Chunxiao Xu, Yanxi Zhang, David A. Scott, Michael J. Eck, Nathanael S. Gray, Pasi A. Janne
Summary: Researchers have discovered a new EGFR inhibitor, JBJ-09-063, which shows efficacy against therapy-resistant mutations in EGFR-mutant lung cancer. The study also found that the resistance to JBJ-09-063 is caused by EGFR homo- or heterodimerization and specific mutations.
Article
Oncology
Po-Lan Su, Jeng-Shiuan Tsai, Szu-Chun Yang, Yi-Lin Wu, Yau-Lin Tseng, Chao-Chun Chang, Yi-Ting Yen, Chia-Ying Lin, Chien-Chung Lin, Chin-Chou Wang, Meng-Chih Lin, Wu-Chou Su
Summary: Osimertinib-based combination therapy showed better overall survival for NSCLC patients with disease progression after osimertinib treatment, supported by synergism with chemotherapy and a higher proportion of apoptosis cells. These findings suggest the potential benefit of osimertinib-based combination therapy and warrant further validation in randomized controlled studies.
Article
Pharmacology & Pharmacy
Po-Yen Chen, Chin-Chou Wang, Chien-Ning Hsu, Chung-Yu Chen
Summary: This study compared the relative survival rate of gefitinib, erlotinib, and afatinib in EGFR-mutated advanced lung adenocarcinoma patients in Taiwan. Afatinib showed better overall survival and time to treatment failure outcomes compared to gefitinib and erlotinib, especially in patients with initial brain metastases.
FRONTIERS IN PHARMACOLOGY
(2021)
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
Ying Cheng, Yong He, Wei Li, He-long Zhang, Qing Zhou, Buhai Wang, Chunling Liu, Andrew Walding, Matilde Saggese, Xiangning Huang, Minhao Fan, Jia Wang, Suresh S. Ramalingam
Summary: The FLAURA China study evaluated the efficacy of first-line osimertinib in Chinese patients with EGFRm advanced NSCLC, showing significant improvements in PFS and OS compared to comparator EGFR TKIs. Safety data were consistent with the known safety profile of osimertinib.
Article
Oncology
Hongjin Chen, Ruixue Xia, Long Jiang, Yong Zhou, Haojun Xu, Weiwei Peng, Chengyun Yao, Guoren Zhou, Yijie Zhang, Hongping Xia, Yongsheng Wang
Summary: The study revealed that overexpression of RhoV in lung adenocarcinoma promotes tumor progression and resistance to EGFR-TKI, potentially worsening patient prognosis. This suggests that RhoV could be a promising therapeutic target for lung adenocarcinoma.
FRONTIERS IN ONCOLOGY
(2021)
Article
Oncology
Mengzhao Wang, James Chih-Hsin Yang, Paul L. Mitchell, Jian Fang, D. Ross Camidge, Weiqi Nian, Chao-Hua Chiu, Jianying Zhou, Yanqiu Zhao, Wu-Chou Su, Tsung-Ying Yang, Viola W. Zhu, Michael Millward, Yun Fan, Wen-Tsung Huang, Ying Cheng, Liyan Jiang, Daniel Brungs, Lyudmila Bazhenova, Chee Khoon Lee, Bo Gao, Yan Xu, Wei-Hsun Hsu, Li Zheng, Pasi A. Janne
Summary: This article reports the discovery and early clinical development of Sunvozertinib (DZD9008), a potential treatment option for EGFRexon20ins NSCLC.
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
Parneet Cheema, Byoung Chul Cho, Helano Freitas, Mariano Provencio, Yuh Min Chen, Sang-We Kim, Yi-Long Wu, Antonio Passaro, Claudio Martin, Marcello Tiseo, Gee-Chen Chang, Keunchil Park, Benjamin Solomon, Otto Burghuber, Janessa Laskin, Ziping Wang, Sung Yong Lee, Yanping Hu, Johan Vansteenkiste, He-long Zhang, Emer Hanrahan, Thomas Geldart, Rosemary Taylor, Leslie Servidio, Jingyi Li, Filippo de Marinis
Summary: This study reports the final analysis from ASTRIS, the largest real-world study of osimertinib in patients with advanced/metastatic EGFR T790M NSCLC. The results demonstrate the clinical benefit and safety of osimertinib in this patient population.
Article
Oncology
Roy S. Herbst, Yi-Long Wu, Thomas John, Christian Grohe, Margarita Majem, Jie Wang, Terufumi Kato, Jonathan W. Goldman, Konstantin Laktionov, Sang-We Kim, Chong-Jen Yu, Huu Vinh Vu, Shun Lu, Kye Young Lee, Guzel Mukhametshina, Charuwan Akewanlop, Filippo de Marinis, Laura Bonanno, Manuel Domine, Frances A. Shepherd, Damien Urban, Xiangning Huang, Ana Bolanos, Marta Stachowiak, Masahiro Tsuboi
Summary: The study demonstrates that adjuvant osimertinib provides a prolonged disease-free survival (DFS) benefit, reduces the risk of recurrence, improves central nervous system (CNS) DFS, and has a consistent safety profile in resected EGFR-mutated NSCLC.
JOURNAL OF CLINICAL ONCOLOGY
(2023)
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
Yan Sun, Liang Zhu, Pian Liu, Huan Zhang, Feng Guo, Xin Jin
Summary: In this study, researchers found that the upregulation of palmitoyl acyltransferase ZDHHC2 is associated with TKI resistance in ccRCC. ZDHHC2 mediates AGK S-palmitoylation to activate the PI3K-AKT-mTOR signaling pathway, which modulates sunitinib sensitivity. These findings suggest that targeting ZDHHC2 may improve the efficacy of sunitinib in treating ccRCC.
Article
Multidisciplinary Sciences
Juliann Chmielecki, Tony Mok, Yi-Long Wu, Ji-Youn Han, Myung-Ju Ahn, Suresh S. Ramalingam, Thomas John, Isamu Okamoto, James Chih-Hsin Yang, Frances A. Shepherd, Krishna C. Bulusu, Gianluca Laus, Barbara Collins, J. Carl Barrett, Ryan J. Hartmaier, Vassiliki Papadimitrakopoulou
Summary: The third-generation EGFR tyrosine kinase inhibitor osimertinib improves progression-free survival compared to platinum-doublet chemotherapy in patients with advanced NSCLC carrying EGFR T790M mutation. In this study, the authors used next-generation sequencing to evaluate the potential mechanisms of acquired resistance to osimertinib in patients from the AURA3 trial. Some patients had undetectable plasma EGFR T790M at disease progression and/or treatment discontinuation.
NATURE COMMUNICATIONS
(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
Biochemistry & Molecular Biology
Lixin He, Jinxin Chen, Pinwei Deng, Shumei Huang, Pian Liu, Chanjuan Wang, Xinjian Huang, Yue Li, Boyu Chen, Dongni Shi, Yunyun Xiao, Xiangfu Chen, Ying Ouyang, Libing Song, Chuyong Lin
Summary: Cyst(e)ine plays a crucial role in the synthesis of glutathione and its storage in lysosomes helps cancer cells maintain redox homeostasis. Breast cancer cells upregulate MFSD12 to increase lysosomal cyst(e)ine storage, which is released to maintain GSH levels and buffer oxidative stress. mTORC1 regulates MFSD12 by phosphorylating residue T254, and this switch modulates lysosomal cyst(e)ine levels in response to oxidative stress, enhancing cell fitness. MFSD12 mutation inhibits its function and suppresses tumor progression, while its overexpression correlates with poor chemotherapy response and prognosis in breast cancer patients.
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)