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Small Cell Lung Cancer Entering the Sphere of Personalized Treatment
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Small Cell Lung Cancer Entering the Sphere of Personalized Treatment

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: 20 May 2025 | Viewed by 3108

Special Issue Editors

Dr. Anna Grenda

E-Mail Website
Guest Editor
Department of Pneumonology, Oncology and Allergology, Medical University of Lublin, Jaczewskiego Street 8, 20-954 Lublin, Poland
Interests: cancer; lung cancer; DNA; RNA; miRNA; epigenetics; NGS; molecular testing
Special Issues, Collections and Topics in MDPI journals
Dr. Michał Szczyrek

E-Mail Website
Guest Editor
Department of Pneumonology, Oncology and Allergology, Medical University in Lublin, 20-950 Lublin, Poland
Interests: lung cancer; oncology; NSCLC; non-small cell lung cancer; SCLC; small cell lung cancer; molecularly targeted therapy; immunotherapy; artificial intelligence
Dr. Izabela Chmielewska

E-Mail Website
Guest Editor
Department of Pneumonology, Oncology and Allergology, Medical University of Lublin, 20-950 Lublin, Poland
Interests: lung cancer; oncology; NSCLC; non-small cell lung cancer; SCLC; small cell lung cancer; molecularly targeted therapy; immunotherapy

Special Issue Information

Dear Colleagues,

Small cell lung cancer (SCLC) is a subtype of lung cancer, which is the most malignant, rapidly progressive and poorly prognostic cancer of the thoracic region. Overall survival is short, and therapeutic options are few. Until recently, the only systemic treatment was chemotherapy, which can cause serious adverse effects and has limited efficacy.

Recently, it became possible to use immune checkpoint inhibitors (ICIs) in combination with chemotherapy in therapy of SCLC patients. This is a big progress in the treatment of small cell lung cancer, where until now not much has been done in terms of modern therapies. Almost in parallel, we have scientific reports regarding broad-spectrum genomic and transcriptomic analysis in SCLC. There have been tremendous molecular advances in SCLC, which may provide the basis for designing and implementing targeted therapies, both with monoclonal antibodies and small-molecule therapies.

We greatly encourage scientific discussion on this very timely, extremely all-important and necessary topic.

Dr. Anna Grenda
Dr. Michał Szczyrek
Dr. Izabela Chmielewska
Guest Editors

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Keywords

  • small cell lung cancer
  • SCLC
  • pathological subtypes
  • molecular subtypes
  • DNA
  • RNA
  • NGS
  • next-generation sequencing transcriptome
  • mutations
  • molecular analysis

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Published Papers (2 papers)

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Research

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14 pages, 1201 KiB  
Article
CD274 (PD-L1) Polymorphisms as Predictors of Efficacy in First-Line Platinum-Based Chemotherapy for Extensive-Stage Small Cell Lung Cancer
by Andrés Barba, Laura López-Vilaró, Malena Ferre, Sergio Martinez-Recio, Margarita Majem, Ivana Sullivan and Juliana Salazar
Int. J. Mol. Sci. 2025, 26(9), 4245; https://doi.org/10.3390/ijms26094245 (registering DOI) - 29 Apr 2025
Abstract
The cornerstone of first-line treatment in extensive-stage small cell lung cancer (ES-SCLC) is platinum- and etoposide-based chemotherapy. Platinum compounds could immunomodulate the tumor microenvironment in addition to their cytotoxic effect. Genetic variation in immune checkpoint (IC) pathways may predict chemotherapy efficacy. Polymorphisms in [...] Read more.
The cornerstone of first-line treatment in extensive-stage small cell lung cancer (ES-SCLC) is platinum- and etoposide-based chemotherapy. Platinum compounds could immunomodulate the tumor microenvironment in addition to their cytotoxic effect. Genetic variation in immune checkpoint (IC) pathways may predict chemotherapy efficacy. Polymorphisms in the IC genes were determined, and their association with survival was analyzed in 78 patients with ES-SCLC treated with chemotherapy. PD-L1 protein expression in tumor tissue was determined. Three variants in CD274 were associated with better median progression-free survival (mPFS): rs2297136 (hazard ratio [HR] 0.52, 95% CI 0.29–0.93; p = 0.03), rs2282055 (HR 0.23, 95% CI 0.09–0.64; p = 0.005), and rs822336 (HR 0.41, 95% CI 0.23–0.73; p = 0.002). CTLA4 rs231775 was also associated with mPFS (HR 0.30, 95% CI 0.14–0.63; p = 0.002). The variants CD274 rs2297136 and CD274 rs822336 were associated with platinum sensitivity (odds ratio [OR] 0.13, 95% CI 0.02–0.70; p = 0.02, and OR 0.08, 95% CI 0.01–0.46; p = 0.005, respectively). CD274 rs2297136 was also associated with better overall survival (p = 0.02), but not after adjustment for covariates. No association was found between CD274 germline variants and PD-L1 tumor expression. Our results suggest that CD274 and CTLA4 variants may be predictive biomarkers for platinum plus etoposide treatment in ES-SCLC. Full article
(This article belongs to the Special Issue Small Cell Lung Cancer Entering the Sphere of Personalized Treatment)

Review

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15 pages, 1009 KiB  
Review
Transitioning to a Personalized Approach in Molecularly Subtyped Small-Cell Lung Cancer (SCLC)
by Anna Grenda, Paweł Krawczyk, Adrian Obara, Łukasz Gajek, Aleksandra Łomża-Łaba and Janusz Milanowski
Int. J. Mol. Sci. 2024, 25(8), 4208; https://doi.org/10.3390/ijms25084208 - 10 Apr 2024
Cited by 4 | Viewed by 2706
Abstract
Lung cancer has become a major public health concern, standing as the leading cause of cancer-related deaths worldwide. Among its subtypes, small-cell lung cancer (SCLC) is characterized by aggressive and rapid growth, poor differentiation, and neuroendocrine features. Typically, SCLC is diagnosed at an [...] Read more.
Lung cancer has become a major public health concern, standing as the leading cause of cancer-related deaths worldwide. Among its subtypes, small-cell lung cancer (SCLC) is characterized by aggressive and rapid growth, poor differentiation, and neuroendocrine features. Typically, SCLC is diagnosed at an advanced stage (extensive disease, ED-SCLC), with distant metastases, and is strongly associated with tobacco smoking and has a poor prognosis. Recent clinical trials, such as CASPIAN and IMpower133, have demonstrated promising outcomes with the incorporation of immune checkpoint inhibitors in first-line chemotherapy, leading to prolonged progression-free survival and overall survival in patients with ED-SCLC compared to standard chemotherapy. Other studies have emphasized the potential for future development of molecularly targeted therapies in SCLC patients, including inhibitors of IGF-1R, DLL3, BCL-2, MYC, or PARP. The molecular subdivision of SCLC based on transcriptomic and immunohistochemical analyses represents a significant advancement in both diagnostic and clinical approaches in SCLC patients. Specific molecular pathways are activated within distinct transcriptome subtypes of SCLC, offering the potential for personalized treatment strategies, such as targeted therapies and immunotherapies. Such tailored approaches hold promise for significantly improving outcomes in SCLC patients. Full article
(This article belongs to the Special Issue Small Cell Lung Cancer Entering the Sphere of Personalized Treatment)
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