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New Advances in Lung Cancer: Diagnosis, Pathophysiology and Emerging Treatments....
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New Advances in Lung Cancer: Diagnosis, Pathophysiology and Emerging Treatments. A Selection of Papers from the 4th Joint Meeting on Lung Cancer of the FHU OncoAge (Nice, France) and the MD Anderson Cancer Center (Houston, TX, USA)

A special issue of Cancers (ISSN 2072-6694).

Deadline for manuscript submissions: 15 January 2025 | Viewed by 10303

Special Issue Editors

Prof. Dr. Paul Hofman

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Guest Editor
FHU OncoAge, IHU RespirERA, University Côte d’Azur, Nice, France
Interests: predictive biomarkers in lung cancer; liquid biopsy; molecular biology; artificial intelligence
Special Issues, Collections and Topics in MDPI journals
Dr. Ignacio I. Wistuba

E-Mail Website
Guest Editor
Department of Translational Molecular Pathology, The University of Texas MD Anderson, Houston, TX, USA
Interests: thoracic oncology
Special Issues, Collections and Topics in MDPI journals
Dr. John Heymach

E-Mail Website
Guest Editor
Department of Thoracic/Head & Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
Interests: thoracic oncology

Special Issue Information

Dear Colleagues,

Lung cancer has become a paradigm for personalized medicine, where identifying disease subtypes through oncogenic driver mutations has led to the development of molecularly targeted therapies. Moreover, the impact of driver oncogenes on the immune tumor microenvironment has profound implications for the effectiveness of immune checkpoint inhibitors. In this regard, there is an urgent need to address obstacles hindering clinical advancements in I-O and targeted therapies, including the development of accurate preclinical models mimicking human immunity and understanding molecular and cellular determinants of primary and secondary resistance. The design of effective combinations of personalized therapies is crucial for individual patient treatment. New treatments such as antibody–drug conjugates (ADCs) could be used in the near future in lung cancer patients, alone or in combination with other therapeutic strategies. These new treatments should be associated with the development of predictive biomarkers. This Special Issue of Cancers focuses on recent topics of interest associated with lung cancer. This follows the 4th joint meeting between different physicians and researchers from both the MD Anderson Cancer Center (Houston, TX, USA), the FHU OncoAge (Nice, France), and the IHU RespirERA (Nice, France). The main objective of this Special Issue is to promote the recent understanding of the development of lung cancer, including new therapeutic strategies and new biomarkers.

Prof. Dr. Paul Hofman
Dr. Ignacio I. Wistuba
Dr. John Heymach
Guest Editors

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 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. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). 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
  • predictive biomarkers
  • liquid biopsy
  • targeted therapy
  • immunotherapy

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Published Papers (6 papers)

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Research

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12 pages, 1159 KiB  
Article
Clinical Interest in Exome-Based Analysis of Somatic Mutational Signatures for Non-Small Cell Lung Cancer
by Morgane Peroz, Hugo Mananet, Nicolas Roussot, Courèche Guillaume Kaderbhai, Valentin Derangère, Caroline Truntzer and François Ghiringhelli
Cancers 2024, 16(17), 3115; https://doi.org/10.3390/cancers16173115 - 9 Sep 2024
Viewed by 917
Abstract
Background: Non-small cell lung cancer (NSCLC) remains the leading cause of cancer-related mortality. This study investigates the clinical interest of whole exome sequencing (WES) for analyzing somatic mutational signatures in patients with advanced or metastatic NSCLC treated with the current standard of care. [...] Read more.
Background: Non-small cell lung cancer (NSCLC) remains the leading cause of cancer-related mortality. This study investigates the clinical interest of whole exome sequencing (WES) for analyzing somatic mutational signatures in patients with advanced or metastatic NSCLC treated with the current standard of care. Methods: Exome sequencing data and clinical characteristics from 132 patients with advanced or metastatic NSCLC were analyzed. Somatic mutational signatures including single base substitutions (SBSs), double base substitutions (DBSs), and copy number signatures were evaluated. Structural variations including tumor mutational burden (TMB), the number of neoantigens, TCR clonality, homologous recombination deficiency (HRD), copy number alterations (CNAs), and microsatellite instability (MSI) score were determined. The association between these genomic features, NSCLC subtypes, and patient outcomes (progression-free and overall survival) was evaluated. Conclusions: Exome sequencing offers valuable insights into somatic mutational signatures in NSCLC. This study identified specific signatures associated with a poor response to immune checkpoint inhibitor (ICI) therapy and chemotherapy, potentially aiding treatment selection and identifying patients unlikely to benefit from these approaches. Full article
(This article belongs to the Special Issue New Advances in Lung Cancer: Diagnosis, Pathophysiology and Emerging Treatments. A Selection of Papers from the 4th Joint Meeting on Lung Cancer of the FHU OncoAge (Nice, France) and the MD Anderson Cancer Center (Houston, TX, USA))
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11 pages, 1839 KiB  
Article
Shifting from Immunohistochemistry to Screen for ALK Rearrangements: Real-World Experience in a Large Single-Center Cohort of Patients with Non-Small-Cell Lung Cancer
by Marius Ilié, Samantha Goffinet, Guylène Rignol, Virginie Lespinet-Fabre, Salomé Lalvée, Olivier Bordone, Katia Zahaf, Christelle Bonnetaud, Kevin Washetine, Sandra Lassalle, Elodie Long-Mira, Simon Heeke, Véronique Hofman and Paul Hofman
Cancers 2024, 16(12), 2219; https://doi.org/10.3390/cancers16122219 - 14 Jun 2024
Viewed by 1507
Abstract
The identification of ALK fusions in advanced non-small-cell lung carcinoma (aNSCLC) is mandatory for targeted therapy. The current diagnostic approach employs an algorithm using ALK immunohistochemistry (IHC) screening, followed by confirmation through ALK FISH and/or next-generation sequencing (NGS). Challenges arise due to the [...] Read more.
The identification of ALK fusions in advanced non-small-cell lung carcinoma (aNSCLC) is mandatory for targeted therapy. The current diagnostic approach employs an algorithm using ALK immunohistochemistry (IHC) screening, followed by confirmation through ALK FISH and/or next-generation sequencing (NGS). Challenges arise due to the infrequency of ALK fusions (3–7% of aNSCLC), the suboptimal specificity of ALK IHC and ALK FISH, and the growing molecular demands placed on small tissue samples, leading to interpretative, tissue availability, and time-related issues. This study investigates the effectiveness of RNA NGS as a reflex test for identifying ALK fusions in NSCLC, with the goal of replacing ALK IHC in the systematic screening process. The evaluation included 1246 NSCLC cases using paired techniques: ALK IHC, ALK FISH, and ALK NGS. ALK IHC identified 51 positive cases (4%), while RNA NGS detected ALK alterations in 59 cases (4.8%). Of the 59 ALK-positive cases identified via NGS, 53 (89.8%) were confirmed to be positive. This included 51 cases detected via both FISH and IHC, and 2 cases detected only via FISH, as they were completely negative according to IHC. The combined reporting time for ALK IHC and ALK FISH averaged 13 days, whereas ALK IHC and RNA NGS reports were obtained in an average of 4 days. These results emphasize the advantage of replacing systematic ALK IHC screening with RNA NGS reflex testing for a more comprehensive and accurate assessment of ALK status. Full article
(This article belongs to the Special Issue New Advances in Lung Cancer: Diagnosis, Pathophysiology and Emerging Treatments. A Selection of Papers from the 4th Joint Meeting on Lung Cancer of the FHU OncoAge (Nice, France) and the MD Anderson Cancer Center (Houston, TX, USA))
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Review

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20 pages, 1170 KiB  
Review
Impact of the Lung Microbiota on Development and Progression of Lung Cancer
by Amine Belaid, Barnabé Roméo, Guylène Rignol, Jonathan Benzaquen, Tanguy Audoin, Valérie Vouret-Craviari, Patrick Brest, Raphaëlle Varraso, Martin von Bergen, Charles Hugo Marquette, Sylvie Leroy, Baharia Mograbi and Paul Hofman
Cancers 2024, 16(19), 3342; https://doi.org/10.3390/cancers16193342 - 29 Sep 2024
Viewed by 1268
Abstract
The past several years have provided a more profound understanding of the role of microbial species in the lung. The respiratory tract is a delicate ecosystem of bacteria, fungi, parasites, and viruses. Detecting microbial DNA, pathogen-associated molecular patterns (PAMPs), and metabolites in sputum [...] Read more.
The past several years have provided a more profound understanding of the role of microbial species in the lung. The respiratory tract is a delicate ecosystem of bacteria, fungi, parasites, and viruses. Detecting microbial DNA, pathogen-associated molecular patterns (PAMPs), and metabolites in sputum is poised to revolutionize the early diagnosis of lung cancer. The longitudinal monitoring of the lung microbiome holds the potential to predict treatment response and side effects, enabling more personalized and effective treatment options. However, most studies into the lung microbiota have been observational and have not adequately considered the impact of dietary intake and air pollutants. This gap makes it challenging to establish a direct causal relationship between environmental exposure, changes in the composition of the microbiota, lung carcinogenesis, and tumor progression. A holistic understanding of the lung microbiota that considers both diet and air pollutants may pave the way to improved prevention and management strategies for lung cancer. Full article
(This article belongs to the Special Issue New Advances in Lung Cancer: Diagnosis, Pathophysiology and Emerging Treatments. A Selection of Papers from the 4th Joint Meeting on Lung Cancer of the FHU OncoAge (Nice, France) and the MD Anderson Cancer Center (Houston, TX, USA))
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17 pages, 2150 KiB  
Review
Liquid and Tissue Biopsies for Lung Cancer: Algorithms and Perspectives
by Paul Hofman
Cancers 2024, 16(19), 3340; https://doi.org/10.3390/cancers16193340 - 29 Sep 2024
Viewed by 1262
Abstract
The targeted therapies and immunotherapies in thoracic oncology, particularly for NS-NSCLC, are associated with an increase in the number of predictive biomarkers to be assessed in routine clinical practice. These treatments are administered thanks to marketing authorization for use in daily practice or [...] Read more.
The targeted therapies and immunotherapies in thoracic oncology, particularly for NS-NSCLC, are associated with an increase in the number of predictive biomarkers to be assessed in routine clinical practice. These treatments are administered thanks to marketing authorization for use in daily practice or are evaluated during clinical trials. Since the molecular targets to be identified are more and more complex and numerous, it is now mandatory to use NGS. NGS can be developed from both tissue and fluid (mainly blood). The blood tests in oncology, so-called “liquid biopsies” (LB), are performed with plasmatic circulating free DNA (cf-DNA) and are complementary to the molecular testing performed with a TB. LB use in lung cancer is associated with international guidelines, but additional algorithms could be set up. However, even if useful for better care of patients, notably with advanced and metastatic NS-NSCLC, until now LB are not often integrated into daily practice, at least in Europe and notably in France. The purpose of this review is to describe the different opportunities and algorithms leading to the identification of the molecular signature of NS-NSCLC, using both tissue and liquid biopsies, and to introduce the principle limitations but also some perspectives in this field. Full article
(This article belongs to the Special Issue New Advances in Lung Cancer: Diagnosis, Pathophysiology and Emerging Treatments. A Selection of Papers from the 4th Joint Meeting on Lung Cancer of the FHU OncoAge (Nice, France) and the MD Anderson Cancer Center (Houston, TX, USA))
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14 pages, 696 KiB  
Review
Early-Stage Non-Small Cell Lung Cancer: New Challenges with Immune Checkpoint Blockers and Targeted Therapies
by Pernelle Lavaud, Martina Bortolot, Lodovica Zullo, David O’Reilly, Jarushka Naidoo, Giannis Mountzios, Olaf Mercier, Lizza E. L. Hendriks and Jordi Remon
Cancers 2024, 16(16), 2779; https://doi.org/10.3390/cancers16162779 - 6 Aug 2024
Viewed by 3503
Abstract
The recent advent of tyrosine kinase inhibitors (TKIs) and immune checkpoint blockers (ICBs) in early-stage non-small cell lung cancer (NSCLC) has dramatically modified treatment strategies by improving the prognosis in this setting. Osimertinib and alectinib, both TKIs, have shown significant improvements in outcomes [...] Read more.
The recent advent of tyrosine kinase inhibitors (TKIs) and immune checkpoint blockers (ICBs) in early-stage non-small cell lung cancer (NSCLC) has dramatically modified treatment strategies by improving the prognosis in this setting. Osimertinib and alectinib, both TKIs, have shown significant improvements in outcomes for patients with resected EGFR- and ALK-positive NSCLC, respectively, changing the standard of care in these subgroups. More recently, the LAURA trial showed the efficacy of osimertinib after chemoradiotherapy in patients with unresectable stage III NSCLC harboring EGFR mutations. Numerous trials are still ongoing to investigate neoadjuvant/perioperative TKIs in several oncogene-driven NSCLC. In addition, several ICBs have been tested and approved as adjuvant (atezolizumab and pembrolizumab), neoadjuvant (nivolumab), and perioperative treatments (pembrolizumab) for patients with resectable early-stage NSCLC. Despite these advances, many challenges remain regarding the use of TKIs and ICBs in this setting, including the optimal duration of adjuvant TKI or induction ICB therapy, the role of minimal residual disease to identify patients at high-risk of disease relapse and to guide adjuvant treatment decisions, and the role of adjuvant chemotherapy in resected oncogene-driven NSCLC. Furthermore, potential predictive biomarkers for efficacy are needed to eventually intensify the entire perioperative strategies. This review aims to summarize and discuss the available evidence, the ongoing trials, and the challenges associated with TKI- and ICB-based approaches in early-stage NSCLC. Full article
(This article belongs to the Special Issue New Advances in Lung Cancer: Diagnosis, Pathophysiology and Emerging Treatments. A Selection of Papers from the 4th Joint Meeting on Lung Cancer of the FHU OncoAge (Nice, France) and the MD Anderson Cancer Center (Houston, TX, USA))
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19 pages, 1259 KiB  
Review
The Multifaceted Role of Neutrophils in NSCLC in the Era of Immune Checkpoint Inhibitors
by Shucheng Miao, Bertha Leticia Rodriguez and Don L. Gibbons
Cancers 2024, 16(14), 2507; https://doi.org/10.3390/cancers16142507 - 10 Jul 2024
Viewed by 1342
Abstract
Lung cancer is the most common cause of cancer-related death in both males and females in the U.S. and non-small-cell lung cancer (NSCLC) accounts for 85%. Although the use of first- or second-line immune checkpoint inhibitors (ICIs) exhibits remarkable clinical benefits, resistance to [...] Read more.
Lung cancer is the most common cause of cancer-related death in both males and females in the U.S. and non-small-cell lung cancer (NSCLC) accounts for 85%. Although the use of first- or second-line immune checkpoint inhibitors (ICIs) exhibits remarkable clinical benefits, resistance to ICIs develops over time and dampens the efficacy of ICIs in patients. Tumor-associated neutrophils (TANs) have an important role in modulating the tumor microenvironment (TME) and tumor immune response. The major challenge in the field is to characterize the TANs in NSCLC TME and understand the link between TAN-related immunosuppression with ICI treatment response. In this review, we summarize the current studies of neutrophil interaction with malignant cells, T-cells, and other components in the TME. Ongoing clinical trials are aimed at utilizing reagents that have putative effects on tumor-associated neutrophils, in combination with ICI. Elevated neutrophil populations and neutrophil-associated factors could be potential therapeutic targets to enhance anti-PD1 treatment in NSCLC. Full article
(This article belongs to the Special Issue New Advances in Lung Cancer: Diagnosis, Pathophysiology and Emerging Treatments. A Selection of Papers from the 4th Joint Meeting on Lung Cancer of the FHU OncoAge (Nice, France) and the MD Anderson Cancer Center (Houston, TX, USA))
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