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NSCLC: from tumorigenesis, immune checkpoint misuse to current and future targeted therapy
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SYSNO ASEP 0584089 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title NSCLC: from tumorigenesis, immune checkpoint misuse to current and future targeted therapy Author(s) Kafkova, L. R. (CZ)
Mierzwicka, Joanna Maria (BTO-N)
Chakraborty, P. (CZ)
Jakubec, P. (CZ)
Fischer, O. (CZ)
Škarda, J. (CZ)
Malý, Petr (BTO-N) RID, ORCID
Raška, M. (CZ)Number of authors 8 Article number 1342086 Source Title Frontiers in Immunology. - : Frontiers Media - ISSN 1664-3224
Roč. 15, FEB 7 2024 (2024)Number of pages 20 s. Language eng - English Country CH - Switzerland Keywords PD-1 ; immune checkpoint ; PD-L1 ; CELL LUNG-CANCER Subject RIV EC - Immunology OECD category Immunology Method of publishing Open access Institutional support BTO-N - RVO:86652036 UT WOS 001169075800001 EID SCOPUS 85185466723 DOI https://doi.org/10.3389/fimmu.2024.1342086 Annotation Non-small cell lung cancer (NSCLC) is largely promoted by a multistep tumorigenesis process involving various genetic and epigenetic alterations, which essentially contribute to the high incidence of mortality among patients with NSCLC. Clinical observations revealed that NSCLC also co-opts a multifaceted immune checkpoint dysregulation as an important driving factor in NSCLC progression and development. For example, a deregulated PI3K/AKT/mTOR pathway has been noticed in 50-70% of NSCLC cases, primarily modulated by mutations in key oncogenes such as ALK, EGFR, KRAS, and others. Additionally, genetic association studies containing patient-specific factors and local reimbursement criteria expose/reveal mutations in EGFR/ALK/ROS/BRAF/KRAS/PD-L1 proteins to determine the suitability of available immunotherapy or tyrosine kinase inhibitor therapy. Thus, the expression of such checkpoints on tumors and immune cells is pivotal in understanding the therapeutic efficacy and has been extensively studied for NSCLC treatments. Therefore, this review summarizes current knowledge in NSCLC tumorigenesis, focusing on its genetic and epigenetic intricacies, immune checkpoint dysregulation, and the evolving landscape of targeted therapies. In the context of current and future therapies, we emphasize the significance of antibodies targeting PD-1/PD-L1 and CTLA-4 interactions as the primary therapeutic strategy for immune system reactivation in NSCLC. Other approaches involving the promising potential of nanobodies, probodies, affibodies, and DARPINs targeting immune checkpoints are also described, these are under active research or clinical trials to mediate immune regulation and reduce cancer progression. This comprehensive review underscores the multifaceted nature, current state and future directions of NSCLC research and treatment Workplace Institute of Biotechnology Contact Monika Kopřivová, Monika.Koprivova@ibt.cas.cz, Tel.: 325 873 700 Year of Publishing 2025 Electronic address https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1342086/full
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