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Cancers
Special Issues
Molecular Advances in Lung Cancer: From Pathogenesis to Precision Therapy
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Molecular Advances in Lung Cancer: From Pathogenesis to Precision Therapy

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Therapy".

Deadline for manuscript submissions: 31 October 2025 | Viewed by 8492

Special Issue Editor

Dr. Federico Pio Fabrizio

E-Mail Website
Guest Editor
Department of Medicine and Surgery, University of Enna "Kore", 94100 Enna, Italy
Interests: lung cancer; immunotherapy; immune checkpoint inhibitors (ICIs); target therapy; tyrosine kinase inhibitors (TKIs); cancer biomarkers
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

We can announce a newly expanded Special Issue of Cancers titled "Molecular Advances in Lung Cancer: From Pathogenesis to Precision Therapy." This Special Issue will comprehensively explore the molecular landscape of lung cancer, bridging fundamental discoveries with clinical applications in precision medicine.

Lung cancer represents a complex and heterogeneous disease driven by diverse molecular alterations. While targeted therapies against EGFR, ALK, ROS1, KRAS, and other oncogenic drivers have revolutionized treatment, emerging research continues to uncover novel molecular mechanisms underlying tumor initiation, progression, and therapeutic resistance. This Special Issue will highlight cutting-edge advances across the entire spectrum of lung cancer research, including the following:

  1. Molecular Pathogenesis: Oncogenic signaling pathways and tumor microenvironment interactions, epigenetic regulation and non-coding RNAs in lung carcinogenesis, and molecular subtypes and tumor heterogeneity;
  2. Diagnostic Innovations: Novel biomarkers for early detection and minimal residual disease, liquid biopsy and next-generation sequencing technologies, and computational approaches for molecular profiling;
  3. Therapeutic Advances: Development of targeted therapies (TKIs, antibody–drug conjugates, etc.), immunotherapy resistance mechanisms and combination strategies, and emerging targets (e.g., MET exon 14, RET, NRG1, HER2);
  4. Translational and Clinical Research: Biomarker-guided clinical trial design, real-world evidence for molecularly matched therapies, and strategies to overcome therapeutic resistance.

We invite original research articles and reviews that contribute to these themes. This Special Issue will provide a platform for multidisciplinary research ranging from basic science to clinical applications, with the ultimate goal of improving outcomes for lung cancer patients worldwide.

All submissions will undergo rigorous peer review to ensure scientific excellence. We look forward to receiving your valuable contributions to this endeavor.

Sincerely,

Dr. Federico Pio Fabrizio
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 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 molecular biology
  • targeted therapy
  • precision medicine
  • biomarkers
  • therapeutic resistance

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Further information on MDPI's Special Issue policies can be found here.

Published Papers (3 papers)

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Research

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13 pages, 966 KiB  
Article
Osimertinib as Second- and ≥Third-Line Treatment in Advanced and Recurrence EGFR-Mutant NSCLC Patients Harboring Acquired T790M Mutation
by Mu-Han Peng, Yen-Hsiang Huang, Kuo-Hsuan Hsu, Jeng-Sen Tseng, Po-Hsin Lee, Kun-Chieh Chen, Gee-Chen Chang and Tsung-Ying Yang
Cancers 2024, 16(24), 4174; https://doi.org/10.3390/cancers16244174 - 14 Dec 2024
Cited by 2 | Viewed by 1435
Abstract
Background/Objectives: Osimertinib is a standard sequential therapy for advanced and recurrent Epidermal Growth Factor Receptor (EGFR)-mutant non-small-cell lung cancer (NSCLC) patients with the T790M mutation, following treatment with first- or second-generation EGFR Tyrosine Kinase Inhibitors (TKIs). This study aims to investigate the differences [...] Read more.
Background/Objectives: Osimertinib is a standard sequential therapy for advanced and recurrent Epidermal Growth Factor Receptor (EGFR)-mutant non-small-cell lung cancer (NSCLC) patients with the T790M mutation, following treatment with first- or second-generation EGFR Tyrosine Kinase Inhibitors (TKIs). This study aims to investigate the differences in clinical outcomes between osimertinib as a 2nd-line treatment and as a ≥3rd-line treatment in this patient population. Methods: Between September 2014 and March 2023, we enrolled advanced and recurrent T790M + NSCLC patients who had received osimertinib as sequential treatment for analysis. All patients had previously been treated with gefitinib, erlotinib, or afatinib as first-line therapy. Results: A total of 158 patients who received osimertinib as sequential treatment were included in the final analysis. Of these, 99 patients (62.7%) received osimertinib as a 2nd-line treatment, while 59 patients (37.3%) were treated with osimertinib as ≥3rd-line therapy. The median progression-free survival (PFS) was 10.7 months for the 2nd-line group and 8.9 months for the ≥3rd-line group. The median overall survival (OS) from first-line treatment was 73.2 months in the 2nd-line group and 57.5 months in the ≥3rd-line group. No statistically significant differences in PFS or OS were observed between the two groups. Conclusions: Our research demonstrated that osimertinib is effective not only as a 2nd-line therapy but also as a ≥3rd-line treatment, offering promising clinical benefits for advanced and recurrent EGFR-mutant NSCLC patients with acquired T790M mutations who have developed resistance to first- and second-generation EGFR-TKI therapy. Full article
(This article belongs to the Special Issue Molecular Advances in Lung Cancer: From Pathogenesis to Precision Therapy)
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11 pages, 871 KiB  
Article
Lazertinib versus Platinum-Based Chemotherapy with Epidermal Growth Factor Receptor (EGFR)-Positive Non-Small-Cell Lung Cancer after Failing EGFR-Tyrosine Kinase Inhibitor: A Real-World External Comparator Study
by Junho Lee, Hyesung Lee, Dongwon Yoon, Eun-Young Choi, Jieun Woo, Bobae Jo, Sohee Kim, Ju-Young Shin and Hyun Ae Jung
Cancers 2024, 16(12), 2169; https://doi.org/10.3390/cancers16122169 - 7 Jun 2024
Cited by 2 | Viewed by 1960
Abstract
Background: Lazertinib is a third-generation tyrosine kinase inhibitor of epidermal growth factor receptor (EGFR-TKI) that selectively inhibit common EGFR mutation and T790M mutation in non-small-cell lung cancer (NSCLC) patients. No previous studies have compared lazertinib to platinum-based chemotherapy. We have compared lazertinib with [...] Read more.
Background: Lazertinib is a third-generation tyrosine kinase inhibitor of epidermal growth factor receptor (EGFR-TKI) that selectively inhibit common EGFR mutation and T790M mutation in non-small-cell lung cancer (NSCLC) patients. No previous studies have compared lazertinib to platinum-based chemotherapy. We have compared lazertinib with platinum-based chemotherapy in EGFR-mutated NSCLC patients after previous EGFR-TKI therapy. Methods: We retrospectively compared 200 patients from LASER201, LASER301, and LASER-PMS studies to 334 patients who were treated with platinum-based chemotherapy after previous EGFR-TKI from the Samsung Medical Center. After propensity score matching (PSM), we selected 156 patients from each group. The primary outcome was progression-free survival (PFS), with overall survival (OS), objective response rate (ORR), and time to treatment discontinuation (TTD) as secondary outcomes. Results: The median follow-up of PFS was 15.61 months in the lazertinib group and 21.67 months in the external control group. The PFS was significantly longer in patients who were treated with lazertinib than those treated with platinum-based chemotherapy (10.97 months vs. 5.10 months; adjusted hazard ratio (HR) 0.40; 95% confidence interval (CI), 0.29–0.55; p < 0.01) after PSM. Lazertinib showed superior OS (32.23 months vs. 18.73 months; adjusted HR 0.45; 95% CI, 0.29–0.69; p < 0.001), ORR (64.1% vs. 47.4%), and TTD (11.66 months vs. 6.73 months; adjusted HR 0.54; 95% CI, 0.39–0.75; p < 0.001) compared to platinum-based chemotherapy. Conclusion: Based on this retrospective, external control study, lazertinib has demonstrated significantly better efficacy compared with platinum-based chemotherapy. The external controls provide important context to evaluate efficacy in single-arm studies. Full article
(This article belongs to the Special Issue Molecular Advances in Lung Cancer: From Pathogenesis to Precision Therapy)
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Review

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35 pages, 1042 KiB  
Review
Optimizing Osimertinib for NSCLC: Targeting Resistance and Exploring Combination Therapeutics
by Yan-You Liao, Chia-Luen Tsai and Hsiang-Po Huang
Cancers 2025, 17(3), 459; https://doi.org/10.3390/cancers17030459 - 29 Jan 2025
Cited by 2 | Viewed by 4409
Abstract
Non-small-cell lung cancer (NSCLC) is a leading cause of cancer-related deaths worldwide, with epidermal growth factor receptor (EGFR) mutations present in a substantial proportion of patients. Third-generation EGFR tyrosine kinase inhibitors (EGFR TKI), exemplified by osimertinib, have dramatically improved outcomes by effectively targeting [...] Read more.
Non-small-cell lung cancer (NSCLC) is a leading cause of cancer-related deaths worldwide, with epidermal growth factor receptor (EGFR) mutations present in a substantial proportion of patients. Third-generation EGFR tyrosine kinase inhibitors (EGFR TKI), exemplified by osimertinib, have dramatically improved outcomes by effectively targeting the T790M mutation—a primary driver of acquired resistance to earlier-generation EGFR TKI. Despite these successes, resistance to third-generation EGFR TKIs inevitably emerges. Mechanisms include on-target mutations such as C797S, activation of alternative pathways like MET amplification, histologic transformations, and intricate tumor microenvironment (TME) alterations. These resistance pathways are compounded by challenges in tolerability, adverse events, and tumor heterogeneity. In light of these hurdles, this review examines the evolving landscape of combination therapies designed to enhance or prolong the effectiveness of third-generation EGFR TKIs. We explore key strategies that pair osimertinib with radiotherapy, anti-angiogenic agents, immune checkpoint inhibitors, and other molecularly targeted drugs, and we discuss the biological rationale, preclinical evidence, and clinical trial data supporting these approaches. Emphasis is placed on how these combinations may circumvent diverse resistance mechanisms, improve survival, and maintain a favorable safety profile. By integrating the latest findings, this review aims to guide clinicians and researchers toward more individualized and durable treatment options, ultimately enhancing both survival and quality of life for patients with EGFR-mutated NSCLC. Full article
(This article belongs to the Special Issue Molecular Advances in Lung Cancer: From Pathogenesis to Precision Therapy)
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