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Oncology
Akihiko Shiiya, Takuro Noguchi, Utano Tomaru, Shin Ariga, Yuta Takashima, Yoshihito Ohhara, Jun Taguchi, Satoshi Takeuchi, Yasushi Shimizu, Ichiro Kinoshita, Tomonobu Koizumi, Yoshihiro Matsuno, Naofumi Shinagawa, Jun Sakakibara-Konishi, Hirotoshi Dosaka-Akita
Summary: EGFR-tyrosine kinase inhibitors induce changes in tumor phenotype and immune escape mechanisms in EGFR-mutant non-small-cell lung cancer cells. These inhibitors upregulate the expression of CD24, an innate immune checkpoint, in EGFR-mutant cells. In addition, EGFR inhibition accelerates the release of cell-free DNA from dying tumor cells, activating interferon signaling pathways. CD24 targeted therapy and cfDNA monitoring may improve treatment outcomes in patients with EGFR-mutant NSCLC.
Article
Biochemistry & Molecular Biology
Ji Hye Kim, Jongwook Kim, Se Seul Im, Ji Hyeon Lee, Sein Hwang, Eun-Ju Chang, Dong-Myung Shin, Jin Kyung Rho, Jaekyoung Son
Summary: The research found that BIX induces apoptotic cell death in EGFR-mutant NSCLC cells and inhibits EGFR signaling, especially in EGFR-TKI resistant cells.
EXPERIMENTAL AND MOLECULAR MEDICINE
(2021)
Article
Oncology
Ryohei Yoshida, Maria Saigi, Tetsuo Tani, Benjamin F. Springer, Hirofumi Shibata, Shunsuke Kitajima, Navin R. Mahadevan, Marco Campisi, William Kim, Yoshihisa Kobayashi, Tran C. Thai, Koji Haratani, Yurie Yamamoto, Shriram K. Sundararaman, Erik H. Knelson, Amir Vajdi, Israel Canadas, Ravindra Uppaluri, Cloud P. Paweletz, Juan J. Miret, Patrick H. Lizotte, Prafulla C. Gokhale, Pasi A. Janne, David A. Barbie
Summary: This study reveals that MET amplification upregulates CD73 to suppress tumor cell STING induction and T-cell responsiveness in TKI-resistant, EGFR-mutated lung cancer, identifying a strategy to enhance immunogenicity and improve treatment.
Article
Multidisciplinary Sciences
Xue Bai, Ze-Qin Guo, Yan-Pei Zhang, Zhen-zhen Fan, Li-Juan Liu, Li Liu, Li-Li Long, Si-Cong Ma, Jian Wang, Yuan Fang, Xin-Ran Tang, Yu-Jie Zeng, Xinghua Pan, De-Hua Wu, Zhong-Yi Dong
Summary: This study finds that LKB1 mutation confers resistance to immune checkpoint blockade therapy in lung adenocarcinoma by impairing the trafficking and adhesion process of activated T cells and suppressing the expression of ICAM1. However, ectopic expression of ICAM1 in LKB1-deficient tumors promotes the activation and homing of CD8(+) T cells, restoring tumor-effector cell interaction and resensitizing tumors to immune checkpoint blockade. Moreover, CDK4/6 inhibitors can upregulate ICAM1 expression in LKB1-deficient cancer cells and enhance the anti-tumor immune response when used in combination with anti-PD-1 antibodies.
NATURE COMMUNICATIONS
(2023)
Article
Cell Biology
Anudari Letian, Eyoel Yemanaberhan Lemma, Paola Cavaliere, Noah Dephoure, Nasser K. Altorki, Timothy E. McGraw
Summary: PD-L1, a transmembrane ligand for immune checkpoint receptor PD1, has been successfully targeted to activate anti-tumor immune response in various solid tumors, including NSCLC. However, only a small percentage of patients respond to the treatment. This study reveals the growth factor control of PD-L1 recycling as a mechanism for regulating PD-L1 density on the plasma membrane, and identifies novel PD-L1 biology specific to mutant EGFR cells. The study also shows that anti-PD-L1 treatment affects mutant EGFR cells differently, leading to reduced cell migration, increased EGFR stability, and increased extracellular vesicle biogenesis.
CELL COMMUNICATION AND SIGNALING
(2023)
Article
Oncology
Wensheng Zhou, Zhichao Liu, Yanan Wang, Yanwei Zhang, Fangfei Qian, Jun Lu, Huimin Wang, Ping Gu, Minjuan Hu, Ya Chen, Zhengyu Yang, Ruiying Zhao, Yuqing Lou, Baohui Han, Wei Zhang
Summary: This study investigated the profile of concomitant alterations in EGFR-mutant LUAD with a size of 3 cm or less and found that TP53 mutation and EGFR amplification were poor prognostic factors for recurrence-free survival.
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
Oncology
Philippe Giron, Carolien Eggermont, Amir Noeparast, Hugo Vandenplas, Erik Teugels, Ramses Forsyth, Olivier De Wever, Pedro Aza-Blanc, Gustavo J. Gutierrez, Jacques De Greve
Summary: The study identifies USP13 as a protein that can increase the sensitivity of lung cancer cells with EGFR mutations to targeted therapy, potentially improving treatment efficacy.
INTERNATIONAL JOURNAL OF CANCER
(2021)
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
Peey-Sei Kok, Kirsty Lee, Sally Lord, Thomas John, Ian Marschner, Yi-Long Wu, Tony S. K. Mok, Chen Khoon Lee
Summary: This study explored the feasibility of incorporating circulating tumor DNA (ctDNA) into the Response Evaluation Criteria in Solid Tumors (RECIST) to provide a more reliable measurement of tumor response. The study found that in patients with EGFR-mutant NSCLC, the absence of detectable ctDNA at week 8 was correlated with improved survival.
Article
Oncology
Kazuya Nishii, Kadoaki Ohashi, Shuta Tomida, Takamasa Nakasuka, Atsuko Hirabae, Sachi Okawa, Jun Nishimura, Hisao Higo, Hiromi Watanabe, Hirohisa Kano, Chihiro Ando, Go Makimoto, Kiichiro Ninomiya, Yuka Kato, Toshio Kubo, Eiki Ichihara, Katsuyuki Hotta, Masahiro Tabata, Shinichi Toyooka, Heiichiro Udono, Yoshinobu Maeda, Katsuyuki Kiura
Summary: EGFR-mutant NSCLC has a noninflamed tumor microenvironment with weak response to immune-checkpoint inhibitors. EGFR-tyrosine kinase inhibitor can induce CD8+ T-cell responses, which are further enhanced by the dual blockade of PD-1 and VEGFR2. These findings could aid in developing alternative immunotherapy strategies for patients with driver mutations and a noninflamed tumor microenvironment.
CANCER IMMUNOLOGY RESEARCH
(2022)
Article
Pharmacology & Pharmacy
Zhen Liu, Xinran Li, Junling Gao, Panpan Yin, Yuou Teng, Peng Yu
Summary: Combination therapy successfully inhibited the EGFR pathway in both wild and mutated types of lung cancer. The combination treatment synergistically induced cell apoptosis by disrupting the balance of Bax and Bcl-xL, loss of mitochondrial membrane potential, and accumulation of reactive oxygen species. Additionally, the combination therapy regulated EGFR downstream signaling pathways. Animal studies confirmed the synergy between the two drugs, and a nano-liposome formulation showed strong cytotoxicity to lung cancer cells.
BIOCHEMICAL PHARMACOLOGY
(2022)
Article
Oncology
Xiuning Le, Cliff Molife, Mark S. S. Leusch, Maria Teresa Rizzo, Patrick M. M. Peterson, Nicola Caria, Yongmei Chen, Elena Gonzalez Gugel, Carla Visseren-Grul
Summary: This observational study explored the impact of TP53 co-mutations on survival in patients with EGFR-mutated advanced non-small cell lung cancer. The results revealed that TP53 co-mutations were associated with decreased survival outcomes, particularly in specific subgroups. These findings suggest that TP53 co-mutations may have a negative effect on the prognosis of patients with EGFR-mutated aNSCLC.
Article
Medicine, Research & Experimental
Shigeki Nanjo, Wei Wu, Niki Karachaliou, Collin M. Blakely, Junji Suzuki, Yu-Ting Chou, Siraj M. Ali, D. Lucas Kerr, Victor R. Olivas, Jonathan Shue, Julia Rotow, Manasi K. Mayekar, Franziska Haderk, Nilanjana Chatterjee, Anatoly Urisman, Jia Chi Yeo, Anders J. Skanderup, Aaron C. Tan, Wai Leong Tam, Oscar Arrieta, Kazuyoshi Hosomichi, Akihiro Nishiyama, Seiji Yano, Yuriy Kirichok, Daniel S. W. Tan, Rafael Rosell, Ross A. Okimoto, Trever G. Bivona
Summary: This study investigates the impact of co-occurring genetic alterations on mutant EGFR and identifies the deficiency of RNA-binding factor RBM10 as a factor that decreases the efficacy of EGFR inhibitors in lung cancer treatment. The study reveals that RBM10 modulates tumor cell apoptosis by regulating the alternative splicing of Bcl-x and its deficiency diminishes EGFR inhibitor-mediated apoptosis. The findings suggest that co-occurring genetic alterations and splicing factor deficiency play a role in determining the sensitivity to targeted kinase inhibitor therapy.
JOURNAL OF CLINICAL INVESTIGATION
(2022)
Article
Multidisciplinary Sciences
Jae-Won Cho, Seyeon Park, Gamin Kim, Heonjong Han, Hyo Sup Shim, Sunhye Shin, Yong-Soo Bae, Seong Yong Park, Sang-Jun Ha, Insuk Lee, Hye Ryun Kim
Summary: This study found that B cells, CXCL13-producing follicular helper CD4(+) T (T-FH)-like cells, and tissue-resident memory CD8(+) T (T-RM)-like cells decreased in EGFR mutant tumors. The proportion of T-RM-like cells is predictive for anti-PD-1 response in NSCLC.
NATURE COMMUNICATIONS
(2021)