Article
Medicine, General & Internal
Xiang-Liang Liu, Ri-Lan Bai, Xiao Chen, Yu-Guang Zhao, Xu Wang, Ke-Wei Ma, Hui-Min Tian, Fu-Jun Han, Zi-Ling Liu, Lei Yang, Wei Li, Fei Gai, Jiu-Wei Cui
Summary: This study utilized a new method, R-superARMS, for semi-quantitative detection of EGFRm in ctDNA in plasma, revealing that the Delta Ct value can predict the sensitivity and efficacy of targeted therapy in EGFRm-positive patients, providing a new approach for personalized clinical treatment.
CHINESE MEDICAL JOURNAL
(2021)
Article
Oncology
Takahiro Yoshizawa, Ken Uchibori, Mitsugu Araki, Shigeyuki Matsumoto, Biao Ma, Ryo Kanada, Yosuke Seto, Tomoko Oh-hara, Sumie Koike, Ryo Ariyasu, Satoru Kitazono, Hironori Ninomiya, Kengo Takeuchi, Noriko Yanagitani, Satoshi Takagi, Kazuma Kishi, Naoya Fujita, Yasushi Okuno, Makoto Nishio, Ryohei Katayama
Summary: This study focused on a lung cancer patient with an EGFR-L747P mutation, which was originally misidentified and resistant to certain EGFR-TKIs. Computational structural analysis was used to investigate the impact of the mutation on the active conformation.
NPJ PRECISION ONCOLOGY
(2021)
Article
Chemistry, Medicinal
Hong-Yi Zhao, Hai-Peng Wang, Yu-Ze Mao, Hao Zhang, Minhang Xin, Xiao-Xiao Xi, Hao Lei, Shuai Mao, Dong-Hui Li, San-Qi Zhang
Summary: This study developed proteolysis targeting chimeras (PROTACs) targeting EGFR mutants by optimizing covalent EGFR ligands to overcome drug resistance in non-small-cell lung cancer (NSCLC). The covalent PROTAC CP17 was discovered to be a highly potent degrader against EGFRL858R/T790M and EGFRdel19 with excellent selectivity. Mechanism investigation showed that the lysosome was involved in the degradation process. Importantly, the covalent binding strategy was proven to be effective for designing PROTACs targeting EGFRL858R/T790M.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Multidisciplinary Sciences
Mengmeng Niu, Jing Xu, Yang Liu, Yuhuang Li, Tao He, Liangping Ding, Yajun He, Yong Yi, Fengtian Li, Rongtian Guo, Ya Gao, Rui Li, Luping Li, Mengyuan Fu, Qingyong Hu, Yangkun Luo, Chunyan Zhang, Kewei Qin, Jianqiao Yi, Shuhan Yu, Jian Yang, Hu Chen, Liang Wang, Zhonghan Li, Biao Dong, Shiqian Qi, Liang Ouyang, Yujun Zhang, Yang Cao, Zhi-Xiong Jim Xiao
Summary: The study shows that FBXL2 targets EGFR and TKI-resistant mutants for degradation, which inhibits EGFR-driven NSCLC growth and TKI resistance.
NATURE COMMUNICATIONS
(2021)
Article
Oncology
Simona Corso, Filippo Pietrantonio, Maria Apicella, Cristina Migliore, Daniela Conticelli, Annalisa Petrelli, Laura D'Errico, Stefania Durando, Daniel Moya-Rull, Sara E. Bellomo, Stefano Ughetto, Maurizio Degiuli, Rossella Reddavid, Uberto Fumagalli, Stefano De Pascale, Giovanni Sgroi, Emanuele Rausa, Gian Luca Baiocchi, Sarah Molfino, Giovanni De Manzoni, Maria Bencivenga, Salvatore Siena, Andrea Sartore-Bianchi, Federica Morano, Salvatore Corallo, Michele Prisciandaro, Maria Di Bartolomeo, Annunziata Gloghini, Silvia Marsoni, Antonino Sottile, Anna Sapino, Caterina Marchio, Asa Dahle-Smith, Zosia Miedzybrodzka, Jessica Lee, Siraj M. Ali, Jeffrey S. Ross, Brian M. Alexander, Vincent A. Miller, Russell Petty, Alexa B. Schrock, Silvia Giordano
Summary: The study highlights EGFR amplification as a driving factor of aggressive behavior and poor prognosis in gastric cancer, with EGFR inhibitors showing activity in patients with EGFR copy number gain. Additionally, the combination of EGFR and mTOR inhibitors shows promise in overcoming primary resistance mechanisms.
CLINICAL CANCER RESEARCH
(2021)
Article
Surgery
Pang-Shuo Perng, Hui-Ping Hsu, Po-Hsuan Lee, Chi-Chen Huang, Chien-Chung Lin, Jung-Shun Lee
Summary: This study aimed to investigate the impact of different mutation loci in surgically treated NSCLC brain metastasis patients. The results showed that EGFR mutations were associated with better survival outcomes in patients with NSCLC brain metastasis. Specifically, the exon 19 deletion mutation was associated with better survival.
ASIAN JOURNAL OF SURGERY
(2023)
Review
Oncology
Yonghui Wu, Kai Zhang, Jiexia Guan, Weibin Wu, Jian Zhang, Huiguo Chen
Summary: Concurrent mutations of EGFR and PIK3CA in non-small cell lung cancer are rare and may complicate treatment. This case report highlights the challenges in managing such cases, as EGFR and PIK3CA concurrent mutations do not respond well to EGFR-TKI treatment. Combination chemotherapy with a TKI may be more effective in this scenario.
CANCER MANAGEMENT AND RESEARCH
(2021)
Review
Biochemistry & Molecular Biology
Hannah L. Tumbrink, Alena Heimsoeth, Martin L. Sos
Summary: EGFR mutations play a major role in druggable targets for lung adenocarcinoma, and optimization of EGFR inhibitors has significantly impacted treatment options. However, the emergence of resistance mutations during drug treatment has driven the need for rapid understanding of individual mutations for developing next-generation inhibitors. The field currently faces a large number of combinations of activating mutations and distinct resistance mutations, alongside the approval of osimertinib as a frontline drug for EGFR-mutant lung cancer.
Article
Oncology
Balazs Gieszer, Zsolt Megyesfalvi, Viktoria Dulai, Judit Papay, Ilona Kovalszky, Jozsef Timar, Janos Fillinger, Tunde Harko, Orsolya Pipek, Vanda Teglasi, Eszter Regos, Gergo Papp, Zoltan Szallasi, Viktoria Laszlo, Ferenc Renyi-Vamos, Gabriella Galffy, Csaba Bodor, Balazs Dome, Judit Moldvay
Summary: This study suggests that high EGFR-aVAF in tumoral tissue predicts benefit from EGFR-TKI treatment in advanced LADC, and that exon 19 EGFR mutation is associated with high EGFR-aVAF and improved survival outcomes.
TRANSLATIONAL LUNG CANCER RESEARCH
(2021)
Article
Respiratory System
Yu Tian, Xiaogang Zhao, Peichao Li, Ming Lu, Hui Tian
Summary: The study revealed that EGFR G873R mutation was significantly associated with better prognosis of docetaxel in non-small cell lung cancer (NSCLC) patients, but not with vinorelbine treatment outcomes and prognosis.
JOURNAL OF THORACIC DISEASE
(2021)
Review
Biochemistry & Molecular Biology
Ahmad Machmouchi, Laudy Chehade, Sally Temraz, Ali Shamseddine
Summary: Targeted monoclonal antibody therapy against EGFR is a leading treatment for mCRC. However, resistance due to KRAS and BRAF mutations has emerged. Cells with these mutations overexpress GLUT1 and SVCT2, leading to intracellular vitamin C transport and cell death. High dose vitamin C shows promise in overcoming EGFR resistance in mCRC with wild KRAS mutation and in patients with KRAS and BRAF mutations, but more clinical trials are needed.
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
Xingyuan Li, Huayan Huang, Yingjia Sun, Qing Jiang, Yongfeng Yu
Summary: This study found that NSCLC patients with positive EGFR mutations after EGFR-TKIs failure who received subsequent immunotherapy plus anti-angiogenesis and chemotherapy are likely to have more benefits in terms of objective response rate, disease control rate, and median progression-free survival.
FRONTIERS IN ONCOLOGY
(2023)
Review
Pharmacology & Pharmacy
Xiaoyu Qian, Xiaodan Guo, Ting Li, Wei Hu, Lin Zhang, Caisheng Wu, Feng Ye
Summary: ICI monotherapy did not improve the overall survival (OS) or progression-free survival (PFS) of patients with EGFR-TKI-resistant NSCLC. However, ICI-based combination therapy showed better PFS and objective response rate (ORR) compared to conventional chemotherapy.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Oncology
Xiaotong Qiu, Yong Wang, Fen Liu, Lihong Peng, Chen Fang, Xiaoyin Qian, Xinwei Zhang, Qian Wang, Zhehao Xiao, Renfang Chen, Shangkun Yuan, Yong Li
Summary: Studies have shown that non-small cell lung cancer patients with EGFR mutations, but with concurrent PIK3CA mutations, treated with EGFR-TKIs have a shorter time to progression and lower overall survival rates.
AMERICAN JOURNAL OF CANCER RESEARCH
(2021)
Review
Neurosciences
Khushnuma Wahabi, Ahmad Perwez, Moshahid A. Rizvi
MOLECULAR NEUROBIOLOGY
(2018)
Article
Chemistry, Multidisciplinary
Babita Aneja, Rizwan Arif, Ahmad Perwez, John V. Napoleon, Phool Hasan, M. Moshahid A. Rizvi, Amir Azam, Rahisuddin, Mohammad Abid
Article
Chemistry, Medicinal
Phool Hasan, Vijay K. Pillalamarri, Babita Aneja, Mohammad Irfan, Mudsser Azam, Ahmad Perwez, Ronan Maguire, Umesh Yadava, Kevin Kavanagh, Constantin G. Daniliuc, Md Belal Ahmad, M. Moshahid A. Rizvi, Qazi Mohd Rizwanul Haq, Anthony Addlagatta, Mohammad Abid
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2019)
Article
Infectious Diseases
Yamini Sharma, Sumit Kumar Rastogi, Ahmad Perwez, Moshahid Alam Rizvi, Nikhat Manzoor
Article
Oncology
Khushnuma Wahabi, Ahmad Perwez, Shabeena Kamarudheen, Zafar Iqbal Bhat, Anurag Mehta, M. Moshahid A. Rizvi
Article
Chemistry, Medicinal
Farah Nawaz, Ozair Alam, Ahmad Perwez, Moshahid A. Rizvi, Mohd J. Naim, Nadeem Siddiqui, Faheem H. Pottoo, Mukund Jha
ARCHIV DER PHARMAZIE
(2020)
Article
Gastroenterology & Hepatology
Raj Ranjan Tiwari, Khushnuma Wahabi, Ahmad Perwez, Zafar Iqbal Bhat, Syed Shamimul Hasan, Sundeep Singh Saluja, Moshahid Alam Rizvi
TURKISH JOURNAL OF GASTROENTEROLOGY
(2020)
Article
Oncology
Farah Nawaz, Ozair Alam, Ahmad Perwez, Moshahid A. Rizvi, Mohd. Javed Naim, Nadeem Siddiqui, Jannat ul Firdaus, Shakilur Rahman, Mukund Jha, Aadil A. Sheikh
Summary: The study evaluated the EGFR kinase inhibitory and anti-proliferative activity of various pyrazole linked pyrazoline derivatives with carbothioamide on human cancer cell lines. Compounds 6h and 6j showed potent inhibitory effects on EGFR kinase and anti-proliferative activity on A549 cell line with KRAS mutation, inducing apoptotic activity. Further exploration is needed in cancer cell lines of different tissue origin and signaling pathways to confirm their potential anticancer activity.
ANTI-CANCER AGENTS IN MEDICINAL CHEMISTRY
(2021)
Review
Biochemistry & Molecular Biology
Ahmad Perwez, Khushnuma Wahabi, Moshahid A. Rizvi
Summary: Parkin, an E3 ubiquitin ligase, is deregulated in various human cancers and plays a crucial role in cancer pathogenesis by controlling major cancer hallmarks. Dysfunction of Parkin leads to genomic instability, perturbed cell cycle, and tumor progression. Existing studies highlight the tumor suppressive potential of Parkin, emphasizing its therapeutic implications and value as a biomarker.
BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER
(2021)
Article
Nanoscience & Nanotechnology
Md Rizwanullah, Ahmad Perwez, Showkat Rasool Mir, Mohd Moshahid Alam Rizvi, Saima Amin
Summary: Polymer-lipid hybrid nanoparticles (PLHNPs) were successfully developed to encapsulate exemestane (EXE) for controlled release, showing promising potential for the effective treatment of breast cancer. The optimized EXE-TPGS-PLHNPs exhibited good physical properties and controlled release behavior, with no significant drug-excipient interactions observed.
Article
Biochemistry & Molecular Biology
Yusra Rahman, Shumaila Afrin, Ahmad Perwez, Mohd Owais Ansari, Tarique Sarwar, Shahbaz Ahmed, Moshahid Alam Rizvi, G. G. Hammad A. Shadab, Mohammad Tabish
Summary: H2 receptor antagonists, such as nizatidine, not only have therapeutic effects on stomach ulcers but also have potential in the healing of malignant ulcers. This study reveals that nizatidine interacts with calf thymus DNA through groove-binding mode and exhibits genotoxic and cytotoxic activities.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Chemistry, Medicinal
Md Jahangir Alam, Ozair Alam, Ahmad Perwez, Moshahid Alam Rizvi, Mohd Javed Naim, Vegi Naidu, Mohd Imran, Mohammed M. Ghoneim, Sultan Alshehri, Faiyaz Shakeel
Summary: In this study, a series of compounds were designed, synthesized, and evaluated for their anti-cancer activity and cytotoxicity. Compound 5o showed excellent cytotoxicity and most of the compounds exhibited drug-like properties.
Article
Oncology
Gary Wildey, Ashley M. Shay, Karen S. McColl, Suzy Yoon, Mohammad A. Shatat, Ahmad Perwez, Kyle B. Spainhower, Adam M. Kresak, MaryBeth Lipka, Michael Yang, Mohadese Behtaj, Pingfu Fu, Asrar Alahmadi, Wadad Mneimneh, Ata Abbas, Afshin Dowlati
Summary: Genomic studies have found that some small cell lung cancer (SCLC) tumors do not have RB1 mutations, contrary to the canonical model. This study examined RB1 protein expression and its function in SCLC and found that 14% of SCLC tumors expressed abundant RB1 protein, which was associated with neuroendocrine gene expression and enriched in YAP1 expression. SCLC cells with RB1 protein expression were sensitive to growth inhibition by the CDK4/6 inhibitor palbociclib, and a patient with wild-type RB1 SCLC showed a significant decrease in mutant TP53 ctDNA allelic fraction and tumor mass after treatment with the CDK4/6 inhibitor abemaciclib.
MOLECULAR CANCER THERAPEUTICS
(2023)
Article
Pharmacology & Pharmacy
Md. Rizwanullah, Ahmad Perwez, Meraj Alam, Shahnawaz Ahmad, Showkat Rasool Mir, Mohd. Moshahid Alam Rizvi, Saima Amin
Summary: This study aimed to develop a novel nanocarrier system, EXE-loaded TPGS-based polymer lipid hybrid nanoparticles (EXE-TPGS-PLHNPs), to enhance the oral bioavailability and anti-breast cancer efficacy of Exemestane (EXE). The results showed that EXE-TPGS-PLHNPs demonstrated significantly higher intestinal permeation compared to EXEPLHNPs and free EXE. Oral administration of EXE-TPGS-PLHNPs and EXE-PLHNPs in Wistar rats resulted in 3.58 and 4.69 times higher oral bioavailability respectively compared to the conventional EXE suspension. Furthermore, EXE-TPGS-PLHNPs and EXE-PLHNPs exhibited better anti-breast cancer activity in Balb/c mice with tumor inhibition rates of 72.72% and 61.94% respectively. Histopathological examination and hematological analysis confirmed the safety of the developed PLHNPs. Therefore, encapsulating EXE in PLHNPs could be a promising approach for oral chemotherapy of breast cancer.
INTERNATIONAL JOURNAL OF PHARMACEUTICS
(2023)
Article
Chemistry, Multidisciplinary
Babita Aneja, Mudsser Azam, Shadab Alam, Ahmad Perwez, Ronan Maguire, Umesh Yadava, Kevin Kavanagh, Constantin G. Daniliuc, M. Moshahid A. Rizvi, Qazi Mohd. Rizwanul Haq, Mohammad Abid