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Current Challenge and Future Advances for Lung Cancer: Genetics, Instrumental...
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Current Challenge and Future Advances for Lung Cancer: Genetics, Instrumental Diagnosis and Treatment 2.0

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Causes, Screening and Diagnosis".

Deadline for manuscript submissions: closed (31 January 2025) | Viewed by 6996

Special Issue Editor

Dr. Giovanni Vicidomini

E-Mail Website
Guest Editor
Thoracic Surgery Unit, University of Campania Luigi Vanvitelli, I-80138 Naples, Italy
Interests: lung cancer; diagnosis; treatment; therapy; surrogate biomarkers; preclinical and translational research
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

This Special Issue is the second edition of the previous Special Issue entitled the "Current Challenge and Future Advances for Lung Cancer: Genetics, Instrumental Diagnosis and Treatment"
(https://www.mdpi.com/journal/cancers/special_issues/Lung_Cancer_Genetics_Instrumental_Diagnosis_Treatment).

Lung cancer remains a malignancy with a poor prognosis, with only 20% of patients reporting an overall survival rate longer than five years from diagnosis. The prognosis of these patients has not significantly improved, despite the developments in the definition of the genetic evolution of lung cancer, the greater accuracy of diagnostic procedures, and the refinement of treatments using multimodal regimens, including surgery, radiotherapy, and systemic therapy (chemotherapy, immunotherapy, and targeted therapy).

Therefore, this Special Issue will include data on potential new diagnostic and therapeutic discoveries that aim to improve the prognosis of lung cancer patients. In particular, the most recent acquisitions regarding the biology of lung cancer (both non-small- and small-cell lung cancer), such as specific gene mutations, genomic heterogeneity, and the discovery of new biomarkers, will be highlighted.

Furthermore, we welcome papers that cover the following topics: (1) developments in diagnostic methods for the early diagnosis of lung cancer, including radiological studies; (2) studies or reviews on innovative aspects of lung cancer treatment in the fields of surgery, radiotherapy, and medical treatments; and (3) studies on real life experiences of multimodal approaches.

Ultimately, for this Special Issue, we welcome basic translational and clinical research papers, studies on cancer biomarkers, professional opinions, and reviews in the broad field of lung cancer diagnosis and therapy in the following categories:

  • Lung cancer diagnosis.
  • Lung cancer metastases (with an emphasis on CNS metastases).
  • Lung cancer surgery.
  • Lung cancer radiotherapy.
  • Lung cancer chemotherapy.
  • Lung cancer target therapies.
  • Lung cancer immunotherapy.
  • Elderly populations with lung cancer.
  • Side effects of lung cancer therapies.
  • Surrogate biomarkers in lung cancer.
  • Preclinical and translational research in lung cancer.

Dr. Giovanni Vicidomini
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
  • diagnosis
  • treatment
  • therapy
  • cancer metastases (with an emphasis on CNS metastases)
  • surgery
  • radiotherapy
  • chemotherapy
  • target therapies
  • immunotherapy
  • elderly with lung cancer
  • side effects
  • surrogate biomarkers
  • preclinical research
  • translational research

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

Published Papers (4 papers)

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Research

12 pages, 497 KiB  
Article
Evaluation of the Quality of Results of Lung Cancer Surgery in France Using the PMSI National Database
by Alain Bernard, Jonathan Cottenet and Catherine Quantin
Cancers 2025, 17(4), 617; https://doi.org/10.3390/cancers17040617 - 11 Feb 2025
Viewed by 708
Abstract
Background. Given the complexity of lung cancer surgery, this study aims to provide an overview of hospitals authorised to perform lung cancer surgery in France, and to assess their performance focusing on severe post-operative complications and 30-day in-hospital mortality based on the [...] Read more.
Background. Given the complexity of lung cancer surgery, this study aims to provide an overview of hospitals authorised to perform lung cancer surgery in France, and to assess their performance focusing on severe post-operative complications and 30-day in-hospital mortality based on the Clavien–Dindo classification (grade > 2). Methods. We included all patients (n = 64,304) who underwent pulmonary resection for lung cancer from the French hospital database (2019–2023). To quantify variations within regions, we used the ratio of the 90th to the 10th decile of the standardised outcome rate of the hospitals. We used a hierarchical logistic regression model to estimate the adjusted odds ratio (aOR) according to the number of annual procedures. We then used the results of this modelling to see how the standardised rate estimate might evolve after simulating a new organisation of hospitals authorised to perform this surgery. Results. A total of 18,151 patients (28%) had severe complications (Clavien–Dindo > 2). Compared to hospital performing less than 100 procedures/year, the risk of severe complications was significantly reduced for hospitals performing between 101 and 250 procedures/year (aOR = 0.83 [0.77–0.89]) and more than 250 procedures/year (aOR = 0.85 [0.77–0.93]). A simulation of hospital reorganisation, using 100 procedures/year as the threshold value, showed that 477 severe complications could have been prevented over the period. Conclusions. This study shows inequalities in performance indicators between hospitals in each French region. The influence of the volume of activity raises questions about the need to restructure the offer of care for complex surgeries, such as lung cancer surgery. Full article
(This article belongs to the Special Issue Current Challenge and Future Advances for Lung Cancer: Genetics, Instrumental Diagnosis and Treatment 2.0)
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18 pages, 8111 KiB  
Article
Combined Therapeutic Strategies Based on the Inhibition of Non-Oncogene Addiction to Improve Tumor Response in EGFR- and KRAS-Mutant Non-Small-Cell Lung Cancer
by Luisa Amato, Daniela Omodei, Caterina De Rosa, Annalisa Ariano, Sara Capaldo, Camilla Carmela Tufano, Rossella Buono, Cristina Terlizzi, Anna Nardelli, Vitale Del Vecchio, Rosanna Palumbo, Concetta Tuccillo, Floriana Morgillo, Federica Papaccio, Virginia Tirino, Francesca Iommelli, Carminia Maria Della Corte and Viviana De Rosa
Cancers 2024, 16(23), 3941; https://doi.org/10.3390/cancers16233941 - 25 Nov 2024
Viewed by 1473
Abstract
Background: Oncogene-driven NSCLC is usually treated with targeted therapies using tyrosine kinase inhibitors (TKIs) to inhibit oncogene downstream signaling pathways, affecting tumor survival and proliferation. EGFR- and KRAS-mutant NSCLCs are the most represented subtypes, and they are treated in clinical practice with oncogene-targeting [...] Read more.
Background: Oncogene-driven NSCLC is usually treated with targeted therapies using tyrosine kinase inhibitors (TKIs) to inhibit oncogene downstream signaling pathways, affecting tumor survival and proliferation. EGFR- and KRAS-mutant NSCLCs are the most represented subtypes, and they are treated in clinical practice with oncogene-targeting drugs in the first and second line, respectively. Unfortunately, the development of oncogene-independent resistant clones limits TKI efficacy. Here, we used non-oncogene addiction (NOA) as an innovative therapeutic strategy to target other essential proteins that support changes in tumor phenotype. Specifically, we tested, for the first time, a combination of inhibitors, namely ATR, involved in DNA damage response, and pyruvate dehydrogenase kinases (PDKs), involved in energy metabolism. Methods: Sensitive PC9 and the corresponding EGFR-TKI-resistant PC9/OR, EGFR-mutant H1975, and KRAS-mutant A549 NSCLC cells, were treated with TKIs (osimertinib and selumetinib, respectively). In parallel, cells were exposed to two combination regimens: one using the TKI with an ATR inhibitor and the other one combining the two selected NOA inhibitors (ATR inhibitor, M4344; and PDK inhibitor, DCA). Results: The effect of these two combined approaches, compared to TKI alone, produced similar results in terms of cell proliferation, cell death, and migration. Thus, depending on tumor biology, selecting between the proposed therapeutic strategies will be different, to maximize tumor response. Conclusions: The major translational relevance of this study is to exploit new targets for the development of innovative and improved therapeutic strategies with NOA drugs, over combinations including target genes within the oncogene pathway, to overcome resistance to TKI therapies in patients with NSCLC who are oncogene-addicted. Full article
(This article belongs to the Special Issue Current Challenge and Future Advances for Lung Cancer: Genetics, Instrumental Diagnosis and Treatment 2.0)
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17 pages, 4106 KiB  
Article
Immune-Cell-Derived Exosomes as a Potential Novel Tool to Investigate Immune Responsiveness in SCLC Patients: A Proof-of-Concept Study
by Luisa Amato, Caterina De Rosa, Viviana De Rosa, Hamid Heydari Sheikhhossein, Annalisa Ariano, Paola Franco, Valeria Nele, Sara Capaldo, Gaetano Di Guida, Filippo Sepe, Alessandra Di Liello, Giuseppe De Rosa, Concetta Tuccillo, Antonio Gambardella, Fortunato Ciardiello, Floriana Morgillo, Virginia Tirino, Carminia Maria Della Corte, Francesca Iommelli and Giovanni Vicidomini
Cancers 2024, 16(18), 3151; https://doi.org/10.3390/cancers16183151 - 14 Sep 2024
Cited by 2 | Viewed by 2594
Abstract
Small cell lung cancer (SCLC) is a highly invasive and rapidly proliferating lung tumor subtype. Most patients respond well to a combination of platinum-based chemotherapy and PD-1/PDL-1 inhibitors. Unfortunately, not all patients benefit from this treatment regimen, and few alternative therapies are available. [...] Read more.
Small cell lung cancer (SCLC) is a highly invasive and rapidly proliferating lung tumor subtype. Most patients respond well to a combination of platinum-based chemotherapy and PD-1/PDL-1 inhibitors. Unfortunately, not all patients benefit from this treatment regimen, and few alternative therapies are available. In this scenario, the identification of new biomarkers and differential therapeutic strategies to improve tumor response becomes urgent. Here, we investigated the role of exosomes (EXs) released from the peripheral blood mononuclear cells (PBMCs) of SCLC patients in mediating the functional crosstalk between the immune system and tumors in response to treatments. In this study, we showed that PBMC-EXs from SCLC patients with different responses to chemoimmunotherapy showed different levels of immune (STING and MAVS) and EMT (Snail and c-Myc) markers. We demonstrated that PBMC-EXs derived from best responder (BR) patients were able to induce a significant increase in apoptosis in SCLC cell lines in vitro compared to PBMC-EXs derived from non-responder (NR) SCLC patients. PBMC-EXs were able to affect cell viability and modulate apoptotic markers, DNA damage and the replication stress pathway, as well as the occurrence of EMT. Our work provides proof of concept that PBMC-EXs can be used as a tool to study the crosstalk between cancer cells and immune cells and that PBMC-EXs exhibit an in vitro ability to promote cancer cell death and reduce tumor aggressiveness. Full article
(This article belongs to the Special Issue Current Challenge and Future Advances for Lung Cancer: Genetics, Instrumental Diagnosis and Treatment 2.0)
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12 pages, 900 KiB  
Article
Enhanced Lung Cancer Detection Using a Combined Ratio of Antigen–Autoantibody Immune Complexes against CYFRA 21-1 and p53
by Heyjin Kim, Jin Kyung Lee, Hye-Ryoun Kim and Young Jun Hong
Cancers 2024, 16(15), 2661; https://doi.org/10.3390/cancers16152661 - 26 Jul 2024
Cited by 1 | Viewed by 1273
Abstract
The early detection of lung cancer (LC) improves patient outcomes, but current methods have limitations. Autoantibodies against tumor-associated antigens have potential as early biomarkers. This study evaluated the 9G testTM Cancer/Lung, measuring circulating complexes of two antigen–autoantibody immune complexes (AIC) against their [...] Read more.
The early detection of lung cancer (LC) improves patient outcomes, but current methods have limitations. Autoantibodies against tumor-associated antigens have potential as early biomarkers. This study evaluated the 9G testTM Cancer/Lung, measuring circulating complexes of two antigen–autoantibody immune complexes (AIC) against their respective free antigens (CYFRA 21-1 and p53) for LC diagnosis. We analyzed 100 LC patients and 119 healthy controls using the 9G testTM Cancer/Lung, quantifying the levels of AICs (CYFRA 21-1-Anti-CYFRA 21-1 autoantibody immune complex (CIC) and p53-Anti-p53 autoantibody immune complex (PIC)), free antigens (CYFRA 21-1 and p53), and ratios of AICs/antigens (LC index). The levels of the CICs and PICs were significantly elevated in LC compared to the controls (p < 0.0062 and p < 0.0026), while free antigens showed no significant difference. The CIC/CYFRA 21-1 and PIC/p53 ratios were also significantly higher in LC (all, p < 0.0001). The LC index, when combining both ratios, exhibited the best diagnostic performance with an area under the curve (AUC) of 0.945, exceeding individual CICs, PICs, and free antigens (AUCs ≤ 0.887). At a cut-off of 3.60, the LC index achieved 81% sensitivity and 95% specificity for LC diagnosis. It detected early-stage (Stage I–II) LC with 87.5% sensitivity, exceeding its performance in advanced stages (72.7%). The LC index showed no significant differences based on age, gender, smoking status (former, current, or never smoker), or pack years smoked. The LC index demonstrates promising potential for early LC diagnosis, exceeding conventional free antigen markers. Full article
(This article belongs to the Special Issue Current Challenge and Future Advances for Lung Cancer: Genetics, Instrumental Diagnosis and Treatment 2.0)
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