Article
Pharmacology & Pharmacy
Haoyue Hu, Songtao Tan, Meng Xie, Peng Guo, Qiang Yu, Juan Xiao, Kangrui Zhao, Qiong Liao, Yi Wang
Summary: In non-small cell lung cancer, concurrent genetic alterations of epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) rearrangements are rare, but their clinical and pathological characteristics are not well-defined, and the optimal treatment approach remains controversial. This report presents a case of stage IV lung adenocarcinoma with both EGFR and ALK mutations, along with high PD-L1 expression. The patient initially received treatment with EGFR tyrosine kinase inhibitors (TKIs), but the disease progressed, and regression was achieved following a switch to ALK-TKI therapy and local radiotherapy. Our report also provides a comprehensive summary of the clinical and pathological features, as well as treatment strategies, for NSCLC patients with concurrent EGFR mutation and ALK rearrangement.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Oncology
Xiao Chu, Yuyin Xu, Ye Li, Yue Zhou, Li Chu, Xi Yang, Jianjiao Ni, Yida Li, Tiantian Guo, Zhiqin Zheng, Qiang Zheng, Qianlan Yao, Yuan Li, Xiaoyan Zhou, Zhengfei Zhu
Summary: This study demonstrates the development of NET in NSCLC without TKI targets or treatments. The under-recognition of this phenomenon may be due to less frequent re-biopsy in these patients. Tissue re-biopsy should be preferred over liquid biopsy for histology transformation consideration. p53/Rb immunohistochemistry may contribute to NET risk prediction in addition to genomic TP53/RB1 evaluation.
Review
Biotechnology & Applied Microbiology
Mercedes L. Dalurzo, Alejandro Aviles-Salas, Fernando Augusto Soares, Yingyong Hou, Yuan Li, Anna Stroganova, Buge Oz, Arif Abdillah, Hui Wan, Yoon-La Choi
Summary: In recent years, the treatment of patients with advanced non-small-cell lung cancer (NSCLC) has been increasingly guided by biomarker testing, particularly focusing on driver genetic alterations involving the epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) rearrangements. However, there are substantial challenges for the implementation of biomarker testing, especially in emerging countries. Understanding the barriers to testing in NSCLC will be key to improving molecular testing rates worldwide and patient outcomes as a result.
ONCOTARGETS AND THERAPY
(2021)
Article
Pathology
Chen Mayer, Efrat Ofek, Danielle Even Fridrich, Yossef Molchanov, Rinat Yacobi, Inbal Gazy, Ido Hayun, Jonathan Zalach, Nurit Paz-Yaacov, Iris Barshack
Summary: ALK and ROS1 gene fusions play important roles in non-small cell lung cancer, and their detection is crucial for patient care. Traditional methods for detection are expensive and time-consuming. This study proposes an alternative method using computer vision deep learning, which can detect ALK and ROS1 fusions accurately and quickly from scanned pathology images. Validation results show that this method performs comparably to traditional diagnostic tests.
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
Biochemistry & Molecular Biology
Nguyen Quoc Khanh Le, Quang Hien Kha, Van Hiep Nguyen, Yung-Chieh Chen, Sho-Jen Cheng, Cheng-Yu Chen
Summary: The study introduced a machine learning model for selecting and predicting EGFR and KRAS mutations in NSCLC patients using a minimal number of semantic radiomics features, with the genetic algorithm plus XGBoost classifier showing the best accuracy in detecting these mutations. This noninvasive machine learning-based model demonstrated robust prediction of EGFR and KRAS mutations in patients with NSCLC.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(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.
Review
Pharmacology & Pharmacy
Dehua Liao, Lun Yu, Dangang Shangguan, Yongchang Zhang, Bowen Xiao, Ni Liu, Nong Yang
Summary: This review provides a summary of the recent therapy advancements in non-small cell lung cancer (NSCLC), focusing on targeted therapies and immunotherapy. It highlights the clinical effects of combination or sequential treatment, offering effective advice for NSCLC treatment.
FRONTIERS IN PHARMACOLOGY
(2022)
Review
Oncology
Roxana Reyes, Noemi Reguart
Summary: Defining the optimal neoadjuvant strategy for early-stage and locoregional (N2) oncogenic-driven lung cancer is a major challenge, with the translation of personalized medicine benefits into earlier-stage disease still far off. Mixed results have been obtained with perioperative tyrosine kinase inhibitors, highlighting the need for further biomarker-driven trials to explore the value of inhibiting oncogenic signaling addiction at earlier stages. Exciting progress is being made in early-stage lung cancer management, with the potential incorporation of novel immunotherapeutic agents as induction strategies showing promising preliminary activity.
TRANSLATIONAL LUNG CANCER RESEARCH
(2021)
Article
Oncology
Norbert Banyi, Deepu Alex, Curtis Hughesman, Kelly McNeil, Diana N. Ionescu, Carmen Ma, Stephen Yip, Barbara Melosky
Summary: The use of Idylla EGFR testing in advanced-stage NSCLC patients could significantly reduce time-to-treatment (TTT). Compared to genetic testing methods, Idylla testing showed a faster turnaround time (TAT) and a high concordance frequency with NGS panel testing. For EGFR-positive patients, the use of Idylla testing led to a 48% reduction in TTT.
Article
Oncology
Yisheng Fang, Yuanyuan Wang, Dongqiang Zeng, Shimeng Zhi, Tingting Shu, Na Huang, Siting Zheng, Jianhua Wu, Yantan Liu, Genjie Huang, Yichen Xue, Jianping Bin, Yulin Liao, Min Shi, Wangjun Liao
Summary: The study found that TKI treatment can remodel the tumor immune microenvironment, leading to significant increases in anti-tumor cell infiltration and cytotoxicity in EGFR/ALK-positive NSCLC samples, while antigen presentation is limited in ALK-rearranged samples. Mutations in the NEFH gene were enriched in samples after TKI treatment, associated with reduced neutrophil infiltration. The immune-associated score generated by hub genes was positively correlated with immune infiltration, immune activation, and a favorable prognosis.
Review
Oncology
Mercedes Herrera-Juarez, Cristina Serrano-Gomez, Helena Bote-de-Cabo, Luis Paz-Ares
Summary: Precision oncology aims to design the best cancer treatment based on tumor biology. In NSCLC, patients with actionable genomic aberrations can benefit from targeted therapy, such as EGFR mutations and ALK rearrangements. Effective inhibitors have been developed for various druggable targets, leading to a paradigm shift in NSCLC treatment.
Article
Biochemistry & Molecular Biology
Baijiao An, Yangyang Fan, Wei Li, Wenyan Nie, Haoran Nie, Mengxuan Wang, Jie Feng, Han Yao, Yin Zhang, Xingshu Li, Geng Tian
Summary: There are currently no effective therapies for non-small cell lung cancer patients with dual mutations in EGFR and ALK, highlighting the urgent need for novel dual-target inhibitors. In this study, a series of highly effective small molecule dual inhibitors of ALK and EGFR were designed, which effectively inhibited both targets in enzymatic and cellular assays. Compound (+)-8l was shown to inhibit the phosphorylation of EGFR and ALK, induce apoptosis and cell cycle arrest, and suppress tumor growth in mouse models.
BIOORGANIC CHEMISTRY
(2023)
Article
Oncology
Lionel Michaux, Alexandre Perrier, Camille Mehlman, Hussa Alshehhi, Antonin Dubois, Roger Lacave, Florence Coulet, Jacques Cadranel, Vincent Fallet
Summary: This article introduces the use of ALK tyrosine kinase inhibitors (ALK TKIs) in ALK-rearranged non-small-cell lung cancer (ALK(+)) and the occurrence of drug resistance mechanisms leading to disease progression. Activation of the EGFR bypass signaling pathway is one uncommon cause of acquired resistance to ALK TKIs. Clinical studies are needed to explore treatment strategies to overcome this drug resistance.
FRONTIERS IN ONCOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Zhonglei Wang, Liyan Yang, Yake Li, Shaohua Song, Juan Qu, Rui He, Shanshan Ren, Peiwei Gong
Summary: A novel nano-system has been developed for the treatment of ALK/EGFR dual-mutant NSCLC. This nano-system addresses the concerns of low drug loading and inefficient drug permeability, providing a foundation for the development of GSH-sensitive nanoparticles for improved drug delivery.
NEW JOURNAL OF CHEMISTRY
(2022)
