Resistance in Lung Cancer Immunotherapy and How to Overcome It: Insights from the Genetics Perspective and Combination Therapies Approach
Lung cancer with the highest number of new cases diagnosed in Europe and in Poland, remains an example of malignancy with a very poor prognosis despite the recent progress in medicine. Different treatment strategies are now available for cancer therapy based on its type, molecular subtype and other...
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MDPI AG
2025-04-01
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| author | Paweł Zieliński Maria Stępień Hanna Chowaniec Kateryna Kalyta Joanna Czerniak Martyna Borowczyk Ewa Dwojak Magdalena Mroczek Grzegorz Dworacki Antonina Ślubowska Hanna Markiewicz Rafał Ałtyn Paula Dobosz |
| author_facet | Paweł Zieliński Maria Stępień Hanna Chowaniec Kateryna Kalyta Joanna Czerniak Martyna Borowczyk Ewa Dwojak Magdalena Mroczek Grzegorz Dworacki Antonina Ślubowska Hanna Markiewicz Rafał Ałtyn Paula Dobosz |
| author_sort | Paweł Zieliński |
| collection | DOAJ |
| description | Lung cancer with the highest number of new cases diagnosed in Europe and in Poland, remains an example of malignancy with a very poor prognosis despite the recent progress in medicine. Different treatment strategies are now available for cancer therapy based on its type, molecular subtype and other factors including overall health, the stage of disease and cancer molecular profile. Immunotherapy is emerging as a potential addition to surgery, chemotherapy, radiotherapy or other targeted therapies, but also considered a mainstay therapy mode. This combination is an area of active investigation in order to enhance efficacy and overcome resistance. Due to the complexity and dynamic of cancer’s ecosystem, novel therapeutic targets and strategies need continued research into the cellular and molecular mechanisms within the tumour microenvironment. From the genetic point of view, several signatures ranging from a few mutated genes to hundreds of them have been identified and associated with therapy resistance and metastatic potential. ML techniques and AI can enhance the predictive potential of genetic signatures and model the prognosis. Here, we present the overview of already existing treatment approaches, the current findings of key aspects of immunotherapy, such as immune checkpoint inhibitors (ICIs), existing molecular biomarkers like PD-L1 expression, tumour mutation burden, immunoscore, and neoantigens, as well as their roles as predictive markers for treatment response and resistance. |
| format | Article |
| id | doaj-art-3decff87807d4a2ca1fa8c45efea642d |
| institution | OA Journals |
| issn | 2073-4409 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj-art-3decff87807d4a2ca1fa8c45efea642d2025-08-20T02:24:42ZengMDPI AGCells2073-44092025-04-0114858710.3390/cells14080587Resistance in Lung Cancer Immunotherapy and How to Overcome It: Insights from the Genetics Perspective and Combination Therapies ApproachPaweł Zieliński0Maria Stępień1Hanna Chowaniec2Kateryna Kalyta3Joanna Czerniak4Martyna Borowczyk5Ewa Dwojak6Magdalena Mroczek7Grzegorz Dworacki8Antonina Ślubowska9Hanna Markiewicz10Rafał Ałtyn11Paula Dobosz12Chair of Pathomorphology and Clinical Immunology, Poznan University of Medical Sciences, 61-701 Poznan, PolandUniversité Paris-Saclay, UVSQ, INSERM, END-ICAP, 94805 Versailles, FranceChair of Pathomorphology and Clinical Immunology, Poznan University of Medical Sciences, 61-701 Poznan, PolandFaculty of Biology, University of Basel, 4123 Basel, SwitzerlandChair of Pathomorphology and Clinical Immunology, Poznan University of Medical Sciences, 61-701 Poznan, PolandDepartment of Endocrinology, Internal Medicine and Metabolism, Poznan University of Medical Sciences, 61-701 Poznan, PolandChair of Pathomorphology and Clinical Immunology, Poznan University of Medical Sciences, 61-701 Poznan, PolandDepartment of Neurology, University Hospital Basel, 4123 Basel, SwitzerlandChair of Pathomorphology and Clinical Immunology, Poznan University of Medical Sciences, 61-701 Poznan, PolandDepartment of Biostatistics and Research Methodology, Faculty of Medicine, Collegium Medicum, Cardinal Stefan Wyszynski University of Warsaw, 02-004 Warsaw, PolandDepartment of Histology and Embryology, Faculty of Medicine, Medical University of Warsaw, 02-004 Warsaw, PolandIT Department, Poznan University of Medical Sciences, 61-701 Poznan, PolandChair of Pathomorphology and Clinical Immunology, Poznan University of Medical Sciences, 61-701 Poznan, PolandLung cancer with the highest number of new cases diagnosed in Europe and in Poland, remains an example of malignancy with a very poor prognosis despite the recent progress in medicine. Different treatment strategies are now available for cancer therapy based on its type, molecular subtype and other factors including overall health, the stage of disease and cancer molecular profile. Immunotherapy is emerging as a potential addition to surgery, chemotherapy, radiotherapy or other targeted therapies, but also considered a mainstay therapy mode. This combination is an area of active investigation in order to enhance efficacy and overcome resistance. Due to the complexity and dynamic of cancer’s ecosystem, novel therapeutic targets and strategies need continued research into the cellular and molecular mechanisms within the tumour microenvironment. From the genetic point of view, several signatures ranging from a few mutated genes to hundreds of them have been identified and associated with therapy resistance and metastatic potential. ML techniques and AI can enhance the predictive potential of genetic signatures and model the prognosis. Here, we present the overview of already existing treatment approaches, the current findings of key aspects of immunotherapy, such as immune checkpoint inhibitors (ICIs), existing molecular biomarkers like PD-L1 expression, tumour mutation burden, immunoscore, and neoantigens, as well as their roles as predictive markers for treatment response and resistance.https://www.mdpi.com/2073-4409/14/8/587lung cancertumour microenvironmentcheckpoint inhibitorsimmunotherapy resistance |
| spellingShingle | Paweł Zieliński Maria Stępień Hanna Chowaniec Kateryna Kalyta Joanna Czerniak Martyna Borowczyk Ewa Dwojak Magdalena Mroczek Grzegorz Dworacki Antonina Ślubowska Hanna Markiewicz Rafał Ałtyn Paula Dobosz Resistance in Lung Cancer Immunotherapy and How to Overcome It: Insights from the Genetics Perspective and Combination Therapies Approach Cells lung cancer tumour microenvironment checkpoint inhibitors immunotherapy resistance |
| title | Resistance in Lung Cancer Immunotherapy and How to Overcome It: Insights from the Genetics Perspective and Combination Therapies Approach |
| title_full | Resistance in Lung Cancer Immunotherapy and How to Overcome It: Insights from the Genetics Perspective and Combination Therapies Approach |
| title_fullStr | Resistance in Lung Cancer Immunotherapy and How to Overcome It: Insights from the Genetics Perspective and Combination Therapies Approach |
| title_full_unstemmed | Resistance in Lung Cancer Immunotherapy and How to Overcome It: Insights from the Genetics Perspective and Combination Therapies Approach |
| title_short | Resistance in Lung Cancer Immunotherapy and How to Overcome It: Insights from the Genetics Perspective and Combination Therapies Approach |
| title_sort | resistance in lung cancer immunotherapy and how to overcome it insights from the genetics perspective and combination therapies approach |
| topic | lung cancer tumour microenvironment checkpoint inhibitors immunotherapy resistance |
| url | https://www.mdpi.com/2073-4409/14/8/587 |
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