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Advances in Lung Cancer Treatment Strategies
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Advances in Lung Cancer Treatment Strategies

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

Deadline for manuscript submissions: 15 March 2026 | Viewed by 1687

Special Issue Editors

Dr. Alessandro Gonfiotti

E-Mail Website
Guest Editor
1. Thoracic Surgery Unit, Careggi University Hospital, 50134 Florence, Italy
2. Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy
Interests: cardiothoracic surgery; radio-guided thoracic surgery; mediastinal tumors surgery; tracheal surgery; minimally invasive thoracic surgery; surgery of mesothelioma; lung cancer staging and treatment; video-assisted sympathectomy for essential hyperhidrosis; surgery of bullous emphysema; lung volume reduction surgery; video-assisted thoracic surgery
Special Issues, Collections and Topics in MDPI journals
Dr. Alice Ravasin

E-Mail Website
Guest Editor Assistant
Thoracic Surgery Unit, Careggi University Hospital, 50134 Florence, Italy
Interests: lung cancer; video-assisted thoracic surgery; chest wall surgery; robotic surgery; mediastinal tumor

Special Issue Information

Dear Colleagues,

Lung cancer remains a major global health challenge, with non-small cell lung cancer (NSCLC) accounting for most diagnoses. Despite progress in individual treatments, outcomes—especially in advanced stages—are still poor. Recent therapeutic advances have transformed treatment paradigms by integrating immunotherapy, targeted agents, and conventional approaches like chemotherapy, radiotherapy, and surgery. The identification of targetable molecular alterations and advances in immune checkpoint inhibitors have enabled highly personalized strategies. A deeper understanding of tumor biology and the immune microenvironment has led to the development of combination therapies customized to the specific molecular characteristics of each patient. Assessment of Programmed Death-Ligand 1 (PD-L1) expression and molecular profiling for driver mutations now play key roles in guiding therapeutic decisions. Integrated treatments are being applied not only in advanced stages but also increasingly in early-stage disease, with the aim of improving survival and quality of life. This Special Issue explores current advances in lung cancer treatment, focusing on clinical progress and innovations and highlighting how multidisciplinary strategies can improve outcomes across all stages.

Dr. Alessandro Gonfiotti
Guest Editor

Dr. Alice Ravasin
Guest Editor Assistant

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 250 words) can be sent to the Editorial Office for assessment.

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
  • immunotherapy
  • immune checkpoint inhibitors
  • chemoimmunotherapy
  • target therapy
  • biomarkers
  • non-small cell lung cancer
  • precision medicine

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Published Papers (2 papers)

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16 pages, 3357 KB  
Article
Cabozantinib Sensitizes NSCLC Cells to Radiation by Inducing Ferroptosis via STAT3/MCL1/BECN1/SLC7A11 Axis Suppression
by Cheng-Yi Wang, Chao-Yuan Huang, Li-Ju Chen, Grace Chen and Shiao-Ya Hong
Cancers 2025, 17(18), 2950; https://doi.org/10.3390/cancers17182950 - 9 Sep 2025
Viewed by 921
Abstract
Background/Objectives: Intrinsic radioresistance in non-small-cell lung cancer (NSCLC) is partially driven by adaptive redox mechanisms that prevent oxidative cell death. Ferroptosis, an iron-dependent form of regulated cell death characterized by lipid peroxidation, has emerged as a potential therapeutic vulnerability in tumors with elevated [...] Read more.
Background/Objectives: Intrinsic radioresistance in non-small-cell lung cancer (NSCLC) is partially driven by adaptive redox mechanisms that prevent oxidative cell death. Ferroptosis, an iron-dependent form of regulated cell death characterized by lipid peroxidation, has emerged as a potential therapeutic vulnerability in tumors with elevated antioxidant capacity. However, its mechanistic integration with radiotherapy remains incompletely understood. Methods: We compared the effects of three clinically approved VEGFR-targeting tyrosine kinase inhibitors (TKIs), cabozantinib, lenvatinib, and ripretinib, on NSCLC cell viability with and without radiation. Subsequent mechanistic studies focused on cabozantinib and included ferroptosis rescue assays (ferrostatin-1, deferoxamine), lipid ROS quantification, glutathione assays, clonogenic survival, co-immunoprecipitation of BECN1–SLC7A11 complexes, and BECN1 knockdown by siRNA and shRNA. Results: All three TKIs were evaluated for cytotoxicity, but only cabozantinib significantly reduced NSCLC cell viability in combination with radiation in a ferroptosis-dependent manner. Cabozantinib inhibited STAT3 phosphorylation and downregulated MCL1, resulting in the release of BECN1. This allowed BECN1 to bind and suppress SLC7A11, disrupting system Xc− function, depleting glutathione, and promoting lipid ROS accumulation. Genetic silencing of BECN1 reversed these effects and restored redox balance and clonogenic capacity. Lenvatinib and ripretinib failed to elicit similar responses, indicating that the inhibition of non-VEGFR targets (e.g., MET, AXL) may be essential for ferroptosis induction by cabozantinib. Conclusions: Cabozantinib enhances the radiosensitization of NSCLC cells through ferroptosis induction mediated by the suppression of the STAT3/MCL1/BECN1/SLC7A11 axis. These findings uncover a novel mechanism linking kinase inhibition to redox imbalance and suggest that the pharmacologic modulation of ferroptosis using multi-target TKIs may represent a rational approach to overcome radioresistance in NSCLC. Full article
(This article belongs to the Special Issue Advances in Lung Cancer Treatment Strategies)
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19 pages, 1379 KB  
Systematic Review
Integrating Surgery and Ablative Therapies for the Management of Multiple Primary Lung Cancer: A Systematic Review
by Zhenghao Dong, Cheng Shen, Jingwen Zhang, Jian Zhou, Xiang Lin, Beinuo Wang and Hu Liao
Cancers 2025, 17(22), 3699; https://doi.org/10.3390/cancers17223699 - 19 Nov 2025
Viewed by 513
Abstract
Background: Multiple primary lung cancer (MPLC) presents clinical challenges due to its biological complexity. While lobectomy remains standard, limited resection and localized ablation offer comparable efficacy. This systematic review evaluates the safety and efficacy of combining surgical and ablative therapies for MPLC. Methods: [...] Read more.
Background: Multiple primary lung cancer (MPLC) presents clinical challenges due to its biological complexity. While lobectomy remains standard, limited resection and localized ablation offer comparable efficacy. This systematic review evaluates the safety and efficacy of combining surgical and ablative therapies for MPLC. Methods: A comprehensive search of PubMed, Embase, and Web of Science (January 2000–2025) identified studies involving MPLC patients treated with both surgery and ablation, either concurrently or sequentially. Data on ablation efficacy, adverse events, and prognosis were extracted. A meta-analysis was performed when data pooling was appropriate. The methodological quality and risk of bias of the included studies were assessed using the MINORS and ROBINS-I tools. Publication bias was evaluated through funnel plots and Egger’s linear regression test. Furthermore, one case report on combination therapy was also included. Results: A total of nine studies met the inclusion criteria and were included in the final analysis. All reported a 100% technical success rate for ablation, efficacy rates exceeding 70%, and adverse event rates ranging from 5.0% to 26.7%. Due to significant heterogeneity among studies, a random-effects model was applied. The meta-analysis yielded a pooled ablation efficacy rate of 97.11% (95% CI: 85.81–100.00%) and a pooled adverse event rate of 14.23% (95% CI: 8.07–20.38%), indicating favorable safety and efficacy of the combined therapy. Conclusions: The integration of surgical and ablative therapies offers a safe and effective strategy for managing MPLC and supports a potential paradigm shift from single-modality treatment toward a more personalized, organ-preserving, and patient-centered approach. Full article
(This article belongs to the Special Issue Advances in Lung Cancer Treatment Strategies)
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