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New Molecular Advances in 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: 30 October 2025 | Viewed by 8646

Special Issue Editor

Special Issue Information

Dear Colleagues,

The treatment of advanced non-small-cell lung cancer has developed in rapid and exciting ways over the last 20 years.

In particular, the importance of identifying molecular activating oncogenes, whose presence may decide treatment with target inhibitors, is well established, bringing better outcomes with good compliance and quality of life. Up till now, for patients affected by advanced non-squamous non-small-cell lung cancer, it is important to identify one of ten activating oncogenes at diagnosis to find the right systemic treatment; furthermore, the mutation has to be confirmed before progression, with consideration of the likelihood of resistance.

In this Special Issue, original research articles and reviews are welcome. Research areas may include (but are not limited to) the following:

  1. Advances in the EGFR pathway, common and uncommon mutations;
  2. Advances in the RET pathway;
  3. Advances in the BRAF pathway, common and uncommon mutations;
  4. Advances in the KRAS pathway;
  5. Advances in the MET pathway;
  6. The role of immune checkpoint inhibitors in oncogene-addicted patients;
  7. Pharmacological interactions with tyrosine kinase inhibitors;
  8. Cardiac toxicity with tyrosine kinase inhibitors;
  9. Advances in the ALK pathway;
  10. The role of radiotherapy in the management of oncogene-addicted disease.

We look forward to receiving your contributions.

Prof. Dr. Alessandra Bearz
Guest Editor

Manuscript Submission Information

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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
  • oncogene
  • tyrosine kinase inhibitors

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Published Papers (3 papers)

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Review

19 pages, 1204 KiB  
Review
Antibody–Drug Conjugates in Non-Small Cell Lung Cancer: State of the Art and Future Perspectives
by Carol Zanchetta, Lorenzo De Marchi, Marianna Macerelli, Giacomo Pelizzari, Jacopo Costa, Giuseppe Aprile and Francesco Cortiula
Int. J. Mol. Sci. 2025, 26(1), 221; https://doi.org/10.3390/ijms26010221 - 30 Dec 2024
Cited by 3 | Viewed by 2489
Abstract
Antibody–drug conjugates (ADCs) represent one of the most promising and rapidly emerging anti-cancer therapies because they combine the cytotoxic effect of the conjugate payload and the high selectivity of the monoclonal antibody, which binds a specific membrane antigen expressed by the tumor cells. [...] Read more.
Antibody–drug conjugates (ADCs) represent one of the most promising and rapidly emerging anti-cancer therapies because they combine the cytotoxic effect of the conjugate payload and the high selectivity of the monoclonal antibody, which binds a specific membrane antigen expressed by the tumor cells. In non-small cell lung cancer (NSCLC), ADCs are being investigated targeting human epidermal growth factor receptor 2 (HER2), human epidermal growth factor receptor 3 (HER3), trophoblast cell surface antigen 2 (TROP2), Mesenchymal–epithelial transition factor (c-MET), and carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5). To date, Trastuzumab deruxtecan is the only ADC that has been approved by the FDA for the treatment of patients with NSCLC, but several ongoing studies, both using ADCs as monotherapy and combined with other therapies, are investigating the efficacy of new ADCs. In this review, we describe the structures and mechanism of action of different ADCs; we present the evidence derived from the main clinical trials investigating ADCs’ efficacy, focusing also on related toxicity; and, finally, we discuss future perspectives in terms of toxicity management, possible biomarkers, and the identification of resistance mechanisms. Full article
(This article belongs to the Special Issue New Molecular Advances in Lung Cancer)
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20 pages, 3364 KiB  
Review
The Role of ctDNA in the Management of Non-Small-Cell Lung Cancer in the AI and NGS Era
by Jacopo Costa, Alexandro Membrino, Carol Zanchetta, Simona Rizzato, Francesco Cortiula, Ciro Rossetto, Giacomo Pelizzari, Giuseppe Aprile and Marianna Macerelli
Int. J. Mol. Sci. 2024, 25(24), 13669; https://doi.org/10.3390/ijms252413669 - 20 Dec 2024
Cited by 3 | Viewed by 3090
Abstract
Liquid biopsy (LB) involves the analysis of circulating tumour-derived DNA (ctDNA), providing a minimally invasive method for gathering both quantitative and qualitative information. Genomic analysis of ctDNA through next-generation sequencing (NGS) enables comprehensive genetic profiling of tumours, including non-driver alterations that offer prognostic [...] Read more.
Liquid biopsy (LB) involves the analysis of circulating tumour-derived DNA (ctDNA), providing a minimally invasive method for gathering both quantitative and qualitative information. Genomic analysis of ctDNA through next-generation sequencing (NGS) enables comprehensive genetic profiling of tumours, including non-driver alterations that offer prognostic insights. LB can be applied in both early-stage disease settings, for the diagnosis and monitoring of minimal residual disease (MRD), and advanced disease settings, for monitoring treatment response and understanding the mechanisms behind disease progression and tumour heterogeneity. Currently, LB has limited use in clinical practice, primarily due to its significant costs, limited diagnostic yield, and uncertain prognostic role. The application of artificial intelligence (AI) in the medical field is a promising approach to processing extensive information and applying it to individual cases to enhance therapeutic decision-making and refine risk assessment. Full article
(This article belongs to the Special Issue New Molecular Advances in Lung Cancer)
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18 pages, 854 KiB  
Review
Navigating Therapeutic Challenges in BRAF-Mutated NSCLC: Non-V600 Mutations, Immunotherapy, and Overcoming Resistance
by Martina Bortolot, Sara Torresan, Elisa De Carlo, Elisa Bertoli, Brigida Stanzione, Alessandro Del Conte, Michele Spina and Alessandra Bearz
Int. J. Mol. Sci. 2024, 25(23), 12972; https://doi.org/10.3390/ijms252312972 - 3 Dec 2024
Cited by 2 | Viewed by 1720
Abstract
Although rare in non-small cell lung cancer (NSCLC), BRAF mutations present considerable therapeutic challenges. While the use of BRAF and MEK inhibitor combinations has significantly improved survival outcomes in patients with BRAF V600E mutations, no targeted therapies are currently available for class II [...] Read more.
Although rare in non-small cell lung cancer (NSCLC), BRAF mutations present considerable therapeutic challenges. While the use of BRAF and MEK inhibitor combinations has significantly improved survival outcomes in patients with BRAF V600E mutations, no targeted therapies are currently available for class II and III mutations, leaving the optimal treatment strategy and prognosis for these patients uncertain. Additionally, despite immunotherapy typically showing limited benefit in patients with other activating genomic alterations, it appears to deliver comparable efficacy in BRAF-mutated NSCLC, emerging as a potentially viable treatment option, particularly in patients with a history of smoking. However, resistance to BRAF pathway inhibitors is inevitable, leading to disease progression, and a well-defined strategy to overcome these resistance mechanisms is lacking. This review aims to explore the critical challenges in the management of BRAF-mutated NSCLC, providing a comprehensive summary of the current evidence and highlighting ongoing clinical trials that aim to address these critical gaps. Full article
(This article belongs to the Special Issue New Molecular Advances in Lung Cancer)
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