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Cancers
Special Issues
Novel Therapeutic Targets for Metastatic Lung Cancer
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Novel Therapeutic Targets for Metastatic Lung Cancer

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

Deadline for manuscript submissions: 31 December 2025 | Viewed by 174

Special Issue Editor

Dr. Andrea De Giglio

E-Mail Website
Guest Editor
1. Department of Medical and Surgical Sciences, University of Bologna, 40138 Bologna, Italy
2. Medical Oncology, IRCCS Azienda Ospedaliero, Universitaria di Bologna, 40138 Bologna, Italy
Interests: thoracic oncology; targeted therapy; immunotherapy; tumor heterogeneity; translational research; drug resistance mechanisms
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Metastatic lung cancer remains a leading cause of cancer-related mortality worldwide, with limited curative options. Recent advances in molecular profiling and immuno-oncology have revealed a variety of novel therapeutic targets beyond classical oncogene drivers, including epigenetic regulators, tumor microenvironment components, and emerging resistance pathways. This Special Issue aims to provide an overview of innovative approaches and recent breakthroughs in identifying and targeting novel vulnerabilities in metastatic lung cancer. We welcome original research articles, reviews, and perspectives exploring new molecular targets, mechanisms of resistance, biomarker development, and strategies to enhance treatment efficacy and overcome immune evasion. Contributions from both preclinical and clinical settings are encouraged.

Dr. Andrea De Giglio
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

  • metastatic lung cancer
  • targeted therapy
  • immunotherapy
  • resistance mechanisms
  • tumor microenvironment
  • biomarkers
  • novel drug targets
  • translational oncology
  • precision medicine
  • epigenetic modulation

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Published Papers (1 paper)

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15 pages, 976 KiB  
Systematic Review
Efficacy and Safety of TROP-2-Targeting Antibody–Drug Conjugate Treatment in Previously Treated Patients with Advanced Non-Small Cell Lung Cancer: A Systematic Review and Pooled Analysis of Reconstructed Patient Data
by Sara Stumpo, Andrea Carlini, Francesco Mantuano, Alessandro Di Federico, Barbara Melotti, Francesca Sperandi, Valentina Favorito and Andrea De Giglio
Cancers 2025, 17(11), 1750; https://doi.org/10.3390/cancers17111750 - 23 May 2025
Viewed by 124
Abstract
Background: Docetaxel is the standard of care for advanced non-small cell lung cancer (NSCLC) after platinum-based chemotherapy and/or immunotherapy but is associated with modest clinical outcomes and considerable toxicity. Sacituzumab govitecan and datopotamab deruxtecan are trophoblast cell surface antigen (TROP)-2-directed antibody–drug conjugates (ADCs) [...] Read more.
Background: Docetaxel is the standard of care for advanced non-small cell lung cancer (NSCLC) after platinum-based chemotherapy and/or immunotherapy but is associated with modest clinical outcomes and considerable toxicity. Sacituzumab govitecan and datopotamab deruxtecan are trophoblast cell surface antigen (TROP)-2-directed antibody–drug conjugates (ADCs) that showed encouraging activity in pretreated patients with advanced NSCLC. This systematic review and pooled analysis aims to comprehensively assess the efficacy and safety of anti-TROP-2 ADCs compared to docetaxel in pretreated patients with advanced NSCLC. Methods: A systematic search through PubMed and EMBASE before 31 January 2025 was performed to identify eligible studies. Randomized controlled phase III trials comparing an anti-TROP-2 regimen to docetaxel in patients with pretreated advanced NSCLC were included. Overall survival (OS), progression-free survival (PFS), and grade ≥ 3 treatment-related adverse events (TRAEs) were extracted from the identified trials. A pooled analysis of reconstructed patient data and meta-analysis employing the random-effect model were used to summarize the efficacy and safety outcomes. Results: Across the two trials included, 1207 patients were enrolled, 598 in the TROP-2 ADC arm and 609 in the docetaxel arm. Anti-TROP-2 treatment did not produce significant improvements in OS (HR: 0.90; 95% CI, 0.78–1.03; P = 0.13) and PFS (HR: 0.84; 95% CI, 0.68–1.02; P = 0.08), compared to docetaxel, even in patients with a nonsquamous histology (OS HR: 0.86; 95% CI, 0.73–1.01; P = 0.06; PFS HR: 0.76; 95% CI, 0.52–1.12; P = 0.17). Across the subgroup analyses, a statistically significant improvement in OS was observed in patients with actionable genomic alterations (AGAs) (HR: 0.63; 95% CI, 0.41–0.95; P = 0.03). Compared to docetaxel, the anti-TROP-2 regimen demonstrated a lower risk of developing grade ≥ 3 TRAEs (RR: 0.76; 95% CI, 0.55–1.05; P = 0.09). Conclusions: The anti-TROP-2 regimen showed a better safety profile but failed to demonstrate a relevant clinical improvement over docetaxel. Anti-TROP-2 ADCs could find a role in the management of patients with AGAs. Full article
(This article belongs to the Special Issue Novel Therapeutic Targets for Metastatic Lung Cancer)
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