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Lung Cancers: An Update on Molecular Diagnostics and Therapy
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Lung Cancers: An Update on Molecular Diagnostics and Therapy

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (20 November 2024) | Viewed by 9044

Special Issue Editor

Dr. Mariusz Chabowski

E-Mail Website
Guest Editor
Department of Surgical Clinical Science, Faculty of Medicine, Wroclaw University of Science and Technology, 50-370 Wroclaw, Poland
Interests: colorectal cancers; thymoma; pulmonary medicine; malignant pleural effusion; video-assisted thoracic surgery; mesothelioma; transthoracic biopsy: bronchoscopy; cancer malnutrition; dietary intervention; cachexia; parenteral nutrition
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Lung cancer is the most common cancer in Poland and world-wide. In 2018, over 2 million new lung cancer cases were diagnosed. Lung cancer is also the leading cause of cancer death. Despite efforts in finding new treatment options, the survival rate of patients with lung cancer remains low. New and innovative treatment paradigms are still being sought. The prognosis of lung cancer depends on the disease stage at diagnosis. The age and sex of the patient and the histologic type of the tumor are also relevant factors. In patients with advanced lung cancer, significant prognostic factors are performance status, fatigue, malnutrition, depression and treatment-related toxicity. Cancer cachexia is associated with a poor prognosis and high risk of death.

This Special Issue is open for submissions from any interested individuals. It is expected that contributions will include original research papers, authoritative and up-to-date reviews, and commentaries on the following topics and areas:

  • Novel drugs and therapeutic approaches for lung cancer;
  • Molecular mechanism for anti-lung cancer or cancer-preventive effects;
  • In vitro, in vivo and clinical studies related to lung cancer at the molecular level;
  • Usage of the therapeutic approaches in conjunction with cancer chemotherapeutic drugs;
  • Challenges and innovative approaches for anti-lung cancer drug development;
  • Novel approaches for lung cancer prevention and intervention;
  • Production of anti-lung cancer agents using biotechnology;
  • Pharmacokinetics and pharmacogenomic studies on anti-lung cancer drugs.

Dr. Mariusz Chabowski
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • lung cancer
  • cancer cachexia
  • prognosis
  • anti-lung cancer agents

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Published Papers (5 papers)

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Research

9 pages, 1264 KiB  
Article
A Prospective Observational Study on Analyzing Lung Cancer Gene Mutation Variant Allele Frequency (VAF) and Its Correlation with Treatment Efficacy
by Yusuke Shinozaki, Kei Morikawa, Hirotaka Kida, Hiroshi Handa, Hisashi Saji, Seiji Nakamura, Yoshiharu Sato, Yumi Ueda, Fumihiko Suzuki, Ryo Matoba and Masamichi Mineshita
Int. J. Mol. Sci. 2024, 25(21), 11694; https://doi.org/10.3390/ijms252111694 - 30 Oct 2024
Viewed by 687
Abstract
A few studies have reported on the variability of the variant allele frequency (VAF) of gene mutations and the relationship between VAF and the therapeutic effect of molecular-targeted drugs. This joint study was conducted from May 2020 to January 2022 between St. Marianna [...] Read more.
A few studies have reported on the variability of the variant allele frequency (VAF) of gene mutations and the relationship between VAF and the therapeutic effect of molecular-targeted drugs. This joint study was conducted from May 2020 to January 2022 between St. Marianna University School of Medicine and the DNA Chip Research Institute. Cytology samples were used to verify the usefulness of a lung cancer compact panel test, which is a high-sensitivity next-generation sequencing (NGS) gene panel test. We analyzed the distribution of VAF and the duration of the initial molecular-targeted drug administration in patients with advanced-stage epidermal growth factor receptor (EGFR) mutations. Of the 196 patients diagnosed with non-small cell carcinoma (NSCLC), gene mutations were detected in 114 (58.2%) cases and in 68.7% of patients with adenocarcinomas (an increased detection rate). A VAF of 30% or more for DNA mutations was confirmed in 35 patients (33.7%), 10% to <30% in 38 (36.5%), and <10% in 31 (29.8%), including 18 patients (17.3%) with <6%, which is considered the lower limit of the LOD for other companion diagnostic kits. EGFR mutations were detected in 59 patients (30%), of whom 35 were in an advanced stage and received molecular-targeted drugs as their initial treatment. Groups A and B comprised patients with a VAF of ≥10% and <10%, respectively, with 27 patients (median VAF 30.6%, range 11.4–77%) in group A and 8 (median VAF 5.4%, range 0.1–8.5%) in group B. The duration of the administration of molecular-targeted drugs was 17 months (range 3–42 months) in group A and 14 months (range 1–45 months) in group B, with no statistically significant difference between the two groups (p-value = 0.7). Twenty-seven percent of patients had a VAF < 10%. Even in patients with a low VAF for gene mutations, sufficient therapeutic effects were observed with molecular-targeted drugs, suggesting the importance of detecting mutations using a highly sensitive method at initial diagnosis. Further prospective validation studies of a larger number of cases are warranted. Full article
(This article belongs to the Special Issue Lung Cancers: An Update on Molecular Diagnostics and Therapy)
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7 pages, 565 KiB  
Communication
Integrating the Idylla™ System Alongside a Real-Time Polymerase Chain Reaction and Next-Generation Sequencing for Investigating Gene Fusions in Pleural Effusions from Non-Small-Cell Lung Cancer Patients: A Pilot Study
by Stefania Scarpino, Alvaro Leone, Dino Galafate, Francesco Pepe, Umberto Malapelle, Sandra Villani, Enrico Giarnieri, Giulio Maurizi, Claudia De Vitis, Rita Mancini, Massimiliano Mancini, Arianna Di Napoli, Andrea Vecchione and Emanuela Pilozzi
Int. J. Mol. Sci. 2024, 25(14), 7594; https://doi.org/10.3390/ijms25147594 - 11 Jul 2024
Viewed by 947
Abstract
Malignant pleural effusion (MPE) from patients with advanced non-small-cell lung cancer (NSCLC) has been proven valuable for molecular analysis; however, simultaneous detection of driver fusions in MPE is still challenging. In this study, we investigated the Idylla™ GeneFusion Panel, a stand-alone test in [...] Read more.
Malignant pleural effusion (MPE) from patients with advanced non-small-cell lung cancer (NSCLC) has been proven valuable for molecular analysis; however, simultaneous detection of driver fusions in MPE is still challenging. In this study, we investigated the Idylla™ GeneFusion Panel, a stand-alone test in tissue samples, in the evaluation of ALK, ROS1, RET and MET ex14 skipping mutations in MPE and compared its performance with routine reference methods (Real-time-based and Next-generation Sequencing—NGS). The inclusion criteria for sample selection were as follows: advanced NSCLC harboring ALK, ROS1, RET fusions or MET exon-skipping alterations and the availability of MPE collected at diagnosis or disease progression. Molecular alterations have been investigated on tissue by fluorescence in situ hybridization (FISH) or Real-time PCR or NGS. For molecular profiling with the Idylla™ GeneFusion, 200 µL of MPE supernatants combined with 50 µL of RNA Later solution were loaded into the Idylla™ cartridge without cfRNA extraction. The Idylla™ GeneFusion Assay performed on MPEs was able to confirm molecular profile, previously diagnosed with conventional methods, in all cases. Our data confirm that MPE are suitable material for investigating fusion alterations. The Idylla™ GeneFusion, although indicated for investigation of tissue samples, offers the possibility of performing a molecular characterization of supernatants without undertaking the entire cfRNA extraction procedure providing a rapid and reliable strategy for the detection of actionable genetic alterations. Full article
(This article belongs to the Special Issue Lung Cancers: An Update on Molecular Diagnostics and Therapy)
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8 pages, 844 KiB  
Communication
Analysis of CYP1B1 Polymorphisms in Lung Cancer Patients Using Novel, Quick and Easy Methods Based on CAPS and ACRS-PCR Techniques
by Adam Dąbrowski, Maciej Nowicki, Aleksandra Budzyńska, Jakub Suchodolski, Rafał Ogórek, Mariusz Chabowski and Katarzyna Przywara
Int. J. Mol. Sci. 2024, 25(12), 6676; https://doi.org/10.3390/ijms25126676 - 18 Jun 2024
Viewed by 1104
Abstract
Within the sequence of the CYP1B1 gene, more than 50 polymorphisms, resulting from single-nucleotide polymorphisms (SNPs), have been described. Some of them play an important role as specific genetic markers in the process of carcinogenesis and for therapeutic purposes. In this publication, we [...] Read more.
Within the sequence of the CYP1B1 gene, more than 50 polymorphisms, resulting from single-nucleotide polymorphisms (SNPs), have been described. Some of them play an important role as specific genetic markers in the process of carcinogenesis and for therapeutic purposes. In this publication, we present methods we have developed that enable the specific and unambiguous identification of four polymorphisms that result in amino acid changes: c. 142C > G, c. 355G > T, c. 1294C > G, and c. 1358A > G. Our studies are based on cleaved amplified polymorphic sequences (CAPSs) and artificially created restriction site (ACRS) PCR techniques; therefore, they require only basic laboratory equipment and low financial outlays. Utilizing the described methods allows for the reduction of research time and cost, and the minimization of errors. Their effectiveness and efficiency depend on the careful design of appropriate primers and the precise selection of suitable restriction enzymes. As a result, further confirmation by sequencing is not necessary. Using the developed method, we examined 63 patients diagnosed with lung cancer and observed a 1.5 to 2.1 times higher frequency of the analyzed single-nucleotide polymorphisms compared to the frequency in the European population. Full article
(This article belongs to the Special Issue Lung Cancers: An Update on Molecular Diagnostics and Therapy)
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19 pages, 1977 KiB  
Article
Mobocertinib in Patients with EGFR Exon 20 Insertion-Positive Non-Small Cell Lung Cancer (MOON): An International Real-World Safety and Efficacy Analysis
by Oliver Illini, Felix Carl Saalfeld, Petros Christopoulos, Michaël Duruisseaux, Anders Vikström, Nir Peled, Ingel Demedts, Elizabeth Dudnik, Anna Eisert, Sayed M. S. Hashemi, Urska Janzic, Waleed Kian, Katja Mohorcic, Saara Mohammed, Maria Silvoniemi, Sacha I. Rothschild, Christian Schulz, Claas Wesseler, Alfredo Addeo, Karin Armster, Malinda Itchins, Marija Ivanović, Diego Kauffmann-Guerrero, Jussi Koivunen, Jonas Kuon, Nick Pavlakis, Berber Piet, Martin Sebastian, Janna-Lisa Velthaus-Rusik, Luciano Wannesson, Marcel Wiesweg, Robert Wurm, Corinna Albers-Leischner, Daniela E. Aust, Melanie Janning, Hannah Fabikan, Sylvia Herold, Anna Klimova, Sonja Loges, Yana Sharapova, Maret Schütz, Christoph Weinlinger, Arschang Valipour, Tobias Raphael Overbeck, Frank Griesinger, Marko Jakopovic, Maximilian J. Hochmair and Martin Wermkeadd Show full author list remove Hide full author list
Int. J. Mol. Sci. 2024, 25(7), 3992; https://doi.org/10.3390/ijms25073992 - 3 Apr 2024
Cited by 3 | Viewed by 3640
Abstract
EGFR exon 20 (EGFR Ex20) insertion mutations in non-small cell lung cancer (NSCLC) are insensitive to traditional EGFR tyrosine kinase inhibitors (TKIs). Mobocertinib is the only approved TKI specifically designed to target EGFR Ex20. We performed an international, real-world safety and efficacy analysis [...] Read more.
EGFR exon 20 (EGFR Ex20) insertion mutations in non-small cell lung cancer (NSCLC) are insensitive to traditional EGFR tyrosine kinase inhibitors (TKIs). Mobocertinib is the only approved TKI specifically designed to target EGFR Ex20. We performed an international, real-world safety and efficacy analysis on patients with EGFR Ex20-positive NSCLC enrolled in a mobocertinib early access program. We explored the mechanisms of resistance by analyzing postprogression biopsies, as well as cross-resistance to amivantamab. Data from 86 patients with a median age of 67 years and a median of two prior lines of treatment were analyzed. Treatment-related adverse events (TRAEs) occurred in 95% of patients. Grade ≥3 TRAEs were reported in 38% of patients and included diarrhea (22%) and rash (8%). In 17% of patients, therapy was permanently discontinued, and two patients died due to TRAEs. Women were seven times more likely to discontinue treatment than men. In the overall cohort, the objective response rate to mobocertinib was 34% (95% CI, 24–45). The response rate in treatment-naïve patients was 27% (95% CI, 8–58). The median progression-free and overall survival was 5 months (95% CI, 3.5–6.5) and 12 months (95% CI, 6.8–17.2), respectively. The intracranial response rate was limited (13%), and one-third of disease progression cases involved the brain. Mobocertinib also showed antitumor activity following EGFR Ex20-specific therapy and vice versa. Potential mechanisms of resistance to mobocertinib included amplifications in MET, PIK3CA, and NRAS. Mobocertinib demonstrated meaningful efficacy in a real-world setting but was associated with considerable gastrointestinal and cutaneous toxicity. Full article
(This article belongs to the Special Issue Lung Cancers: An Update on Molecular Diagnostics and Therapy)
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20 pages, 4762 KiB  
Article
Detailed Characterization of the Lung–Gut Microbiome Axis Reveals the Link between PD-L1 and the Microbiome in Non-Small-Cell Lung Cancer Patients
by Vytautas Ankudavicius, Darja Nikitina, Rokas Lukosevicius, Deimante Tilinde, Violeta Salteniene, Lina Poskiene, Skaidrius Miliauskas, Jurgita Skieceviciene, Marius Zemaitis and Juozas Kupcinskas
Int. J. Mol. Sci. 2024, 25(4), 2323; https://doi.org/10.3390/ijms25042323 - 15 Feb 2024
Cited by 3 | Viewed by 1753
Abstract
Next-generation sequencing technologies have started a new era of respiratory tract research in recent years. Alterations in the respiratory microbiome between healthy and malignant conditions have been revealed. However, the composition of the microbiome varies among studies, even in similar medical conditions. Also, [...] Read more.
Next-generation sequencing technologies have started a new era of respiratory tract research in recent years. Alterations in the respiratory microbiome between healthy and malignant conditions have been revealed. However, the composition of the microbiome varies among studies, even in similar medical conditions. Also, there is a lack of complete knowledge about lung–gut microbiome interactions in lung cancer patients. The aim of this study was to explore the lung–gut axis in non-small-cell lung cancer (NSCLC) patients and the associations between lung–gut axis microbiota and clinical parameters (CRP, NLR, LPS, CD8, and PD-L1). Lung tissue and fecal samples were used for bacterial 16S rRNA sequencing. The results revealed, for the first time, that the bacterial richness in lung tumor tissue gradually decreased with an increase in the level of PD-L1 expression (p < 0.05). An analysis of β-diversity indicated a significant positive correlation between the genera Romboutsia and Alistipes in both the lung tumor biopsies and stool samples from NSCLC patients (p < 0.05). Survival analysis showed that NSCLC patients with higher bacterial richness in their stool samples had prolonged overall survival (HR: 2.06, 95% CI: 1.025–4.17, p = 0.0426). Full article
(This article belongs to the Special Issue Lung Cancers: An Update on Molecular Diagnostics and Therapy)
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