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Advances in the Diagnosis and Treatment of Non-small Cell Lung Cancer

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Oncology".

Deadline for manuscript submissions: 20 February 2025 | Viewed by 3784

Special Issue Editor


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Guest Editor
Department of Genetics and Clinical Immunology, National Institute of Tuberculosis and Lung Diseases, 01-138 Warsaw, Poland
Interests: lung cancer; targeted treatments; molecular profiling; circulating tumor DNA and RNA; FGFR mutations; EGFR mutations

Special Issue Information

Dear Colleagues,

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related deaths worldwide. Unfortunately, the majority of patients are diagnosed with advanced disease, leading to an unfavorable prognosis. Recent studies have demonstrated the involvement of essential genes and signaling pathways in the tumorigenesis and progression of NSCLC. A better understanding of this malignancy has led to the discovery of novel molecular therapeutic strategies. Both targeted therapies and immunotherapies have improved prognoses and substantially prolonged the progression-free survival of patients with advanced NSCLC. However, treatment non-responsiveness and rapid disease progression appearing in some patients are challenging.

Currently, targeted treatment therapies for advanced NSCLC patients are based on a wide range of established and emerging molecular biomarkers. The advent and wide-scale implementation of next-generation sequencing (NGS) technologies can contribute to the discovery of a broad range of genetic alterations, particularly those influencing treatment sensitivity and those underlying primary, adaptive, and acquired resistance within cancer cells.

Therefore, we anticipate that this IJMS Special Issue will serve as a compendium of cutting-edge insights, enhancing our understanding of NSCLC. We invite submissions of original research articles as well as reviews in the areas of basic, translational, and clinical NSCLC research. Except for pure clinical studies, we welcome clinical or theoretical model submissions with biomolecular experiments encompassing all aspects of NSCLC. Specifically, we encourage contributions to the following key areas of research:

  • Non-small cell lung cancer;
  • Precision medicine applications in NSCLC;
  • Targeted therapy for NSCLC;
  • Immunotherapy in NSCLC;
  • Novel therapeutic agents in lung cancer;
  • Tumor drug resistance in lung cancer;
  • Molecular diagnostic techniques in NSCLC;
  • Lung cancer biomarkers—identification and validation;
  • Molecular genetics and proteomics in NSCLC;
  • Lung cancer pathogenesis;
  • Next-generation sequencing (NGS) in lung cancer research.

Dr. Joanna Moes-Sosnowska
Guest Editor

Manuscript Submission Information

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Keywords

  • non-small cell lung cancer
  • precision medicine applications in NSCLC
  • targeted therapy for NSCLC
  • immunotherapy in NSCLC
  • novel therapeutic agents in lung cancer
  • tumor drug resistance in lung cancer
  • molecular diagnostic techniques in NSCLC
  • lung cancer biomarkers—identification and validation
  • molecular genetics and proteomics in NSCLC
  • lung cancer pathogenesis
  • next-generation sequencing (NGS) in lung cancer research

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Published Papers (3 papers)

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20 pages, 2631 KiB  
Article
The Detailed Analysis of Polish Patients with Non-Small Cell Lung Cancer Through Insights from Molecular Testing (POL-MOL Study)
by Dariusz M. Kowalski, Magdalena Zaborowska-Szmit, Maciej Bryl, Agnieszka Byszek, Dariusz Adam Dziedzic, Piotr Jaśkiewicz, Renata Langfort, Maciej Krzakowski, Tadeusz Orłowski, Rodryg Ramlau and Sebastian Szmit
Int. J. Mol. Sci. 2024, 25(21), 11354; https://doi.org/10.3390/ijms252111354 - 22 Oct 2024
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Abstract
Molecular testing is recommended in patients with metastatic non-small cell lung cancer (NSCLC), but the extent of its use in Poland is unknown. The aim of the POL-MOL study was to investigate the frequency of using molecular testing in Polish patients with NSCLC. [...] Read more.
Molecular testing is recommended in patients with metastatic non-small cell lung cancer (NSCLC), but the extent of its use in Poland is unknown. The aim of the POL-MOL study was to investigate the frequency of using molecular testing in Polish patients with NSCLC. The invited Polish oncologists completed two questionnaires, and data for 1001 patients undergoing systemic treatment for NSCLC were collected. The use of molecular tests for the following genetic mutations was recorded: EGFR (del19, sub21), EGFR (other than del19/sub21), EGFR T790M, ALK (expression and rearrangement), RET, NTRK, ROS1, BRAF, HER2, and MET, as well as for immunochemical assessment of programmed cell death ligand 1 (PD-L1). Thanks to the weighting procedure, the results are representative of the population of Polish patients treated for NSCLC. Molecular tests were applied in 78% of patients with NSCL, 70% of patients with NSCLC not otherwise specified, and in 12% of patients with squamous cell carcinoma of the lung. The frequency of application increased with disease stage in all groups. In patients with squamous cell carcinoma, approximately 30% of tests for EGFR, ALK, and RET mutations were positive, which confirms the importance of testing at least a preselected subgroup of patients. Full article
(This article belongs to the Special Issue Advances in the Diagnosis and Treatment of Non-small Cell Lung Cancer)
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18 pages, 833 KiB  
Article
The Advantage of Targeted Next-Generation Sequencing over qPCR in Testing for Druggable EGFR Variants in Non-Small-Cell Lung Cancer
by Adam Szpechcinski, Joanna Moes-Sosnowska, Paulina Skronska, Urszula Lechowicz, Magdalena Pelc, Malgorzata Szolkowska, Piotr Rudzinski, Emil Wojda, Krystyna Maszkowska-Kopij, Renata Langfort, Tadeusz Orlowski, Pawel Sliwinski, Mateusz Polaczek and Joanna Chorostowska-Wynimko
Int. J. Mol. Sci. 2024, 25(14), 7908; https://doi.org/10.3390/ijms25147908 - 19 Jul 2024
Viewed by 1270
Abstract
The emergence of targeted therapies in non-small-cell lung cancer (NSCLC), including inhibitors of epidermal growth factor receptor (EGFR) tyrosine kinase, has increased the need for robust companion diagnostic tests. Nowadays, detection of actionable variants in exons 18–21 of the EGFR gene by qPCR [...] Read more.
The emergence of targeted therapies in non-small-cell lung cancer (NSCLC), including inhibitors of epidermal growth factor receptor (EGFR) tyrosine kinase, has increased the need for robust companion diagnostic tests. Nowadays, detection of actionable variants in exons 18–21 of the EGFR gene by qPCR and direct DNA sequencing is often replaced by next-generation sequencing (NGS). In this study, we evaluated the diagnostic usefulness of targeted NGS for druggable EGFR variants testing in clinical NSCLC material previously analyzed by the IVD-certified qPCR test with respect to DNA reference material. We tested 59 NSCLC tissue and cytology specimens for EGFR variants using the NGS ‘TruSight Tumor 15’ assay (Illumina) and the qPCR ‘cobas EGFR mutation test v2’ (Roche Diagnostics). The sensitivity and specificity of targeted NGS assay were evaluated using the biosynthetic and biological DNA reference material with known allelic frequencies (VAF) of EGFR variants. NGS demonstrated a sufficient lower detection limit for diagnostic applications (VAF < 5%) in DNA reference material; all EGFR variants were correctly identified. NGS showed high repeatability of VAF assessment between runs (CV% from 0.02 to 3.98). In clinical material, the overall concordance between NGS and qPCR was 76.14% (Cohen’s Kappa = 0.5933). The majority of discordant results concerned false-positive detection of EGFR exon 20 insertions by qPCR. A total of 9 out of 59 (15%) clinical samples showed discordant results for one or more EGFR variants in both assays. Additionally, we observed TP53 to be a frequently co-mutated gene in EGFR-positive NSCLC patients. In conclusion, targeted NGS showed a number of superior features over qPCR in EGFR variant detection (exact identification of variants, calculation of allelic frequency, high analytical sensitivity), which might enhance the basic diagnostic report. Full article
(This article belongs to the Special Issue Advances in the Diagnosis and Treatment of Non-small Cell Lung Cancer)
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7 pages, 1869 KiB  
Case Report
Prolonged Response to Afatinib and Crizotinib in a Rare Case of EGFR-, HER2-, MET- and ROS1-Alterated Lung Adenocarcinoma
by Eva Plomer, Martin Früh, Arno Lauber, Izadora Demmer, Wolfram Jochum and Kira-Lee Koster
Int. J. Mol. Sci. 2024, 25(11), 5698; https://doi.org/10.3390/ijms25115698 - 23 May 2024
Cited by 1 | Viewed by 1152
Abstract
We present the case of a 70-year-old never-smoking female patient with epidermal growth factor receptor (EGFR) p.L858R-mutated metastatic non-small cell lung cancer (NSCLC). After three months of first-line treatment with erlotinib, progression occurred and platinum/pemetrexed was initiated, followed by a response [...] Read more.
We present the case of a 70-year-old never-smoking female patient with epidermal growth factor receptor (EGFR) p.L858R-mutated metastatic non-small cell lung cancer (NSCLC). After three months of first-line treatment with erlotinib, progression occurred and platinum/pemetrexed was initiated, followed by a response for more than two years. After the progression, the molecular testing of a vertebral metastasis revealed a ROS proto-oncogene 1 (ROS1) translocation and a human epidermal growth factor receptor 2 (HER2) p.S310F mutation, in addition to the known EGFR p.L858R mutation. Crizotinib then led to a durable response of 17 months. The molecular retesting of the tumour cells obtained from the recurrent pleural effusion revealed the absence of the ROS1 translocation, whereas the EGFR and HER2 mutations were still present. Afatinib was added to the crizotinib, and the combination treatment resulted in another durable response of more than two years. The patient died more than 7 years after the initial diagnosis of metastatic NSCLC. This case demonstrates that the repeated molecular testing of metastatic NSCLC may identify new druggable genomic alterations that can impact the patient management and improve the patient outcome. Full article
(This article belongs to the Special Issue Advances in the Diagnosis and Treatment of Non-small Cell Lung Cancer)
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