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Transcription Factors in Lung Cancer: Mechanisms and Future Perspectives

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (15 April 2024) | Viewed by 6911

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Dr. Kostas A. Papavassiliou

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First University Department of Respiratory Medicine, 'Sotiria' Hospital, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece
Interests: respiratory medicine; tumor biology; molecular oncology; lung carcinogenesis; transcription factors; cancer cell signaling

Prof. Dr. Athanasios G. Papavassiliou

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Guest Editor

Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 115 27 Athens, Greece
Interests: molecular medicine; cancer mechanobiology; regulation of gene expression; transcription factors in health and disease; epigenetics; signal transduction; mechanotransduction
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Dear Colleagues,

The management of lung cancer has undergone revolutionary changes in the last few years. Advancements in our understanding of the molecular underpinnings of lung cancer have allowed for the development of several targeted therapies and immunotherapies. Nevertheless, lung cancer is a highly heterogeneous disease and the development of resistance to current therapies leads to disease recurrence and poor prognosis.

Transcription factors are major proteins located at the bottleneck of signaling pathways, which orchestrate a multitude of physiological cellular processes, including proliferation, differentiation, apoptosis, self-renewal, and migration. When transcription factors are deregulated they can promote the initiation and development of different cancer types. Recent research has revealed the implication of aberrant transcription factors in the two major types of lung cancer, NSCLC and SCLC. Identifying which and how individual transcription factors with oncogenic or tumor-suppressive functions contribute to lung cancer will potentially result in the development of novel therapeutics that are able to prolong the survival of lung cancer patients. Transcription-factor-targeting drugs could also be combined with other targeted therapies, immune checkpoint inhibitors, or radiotherapy in a synergistic fashion or to overcome resistance to current therapies. Additionally, transcription factors may be utilized as prognostic and predictive biomarkers for the treatment of lung cancer.

Since transcription factors act in concert with other proteins, including different transcription factors, coactivators, and corepressors, research efforts should also be focused on elucidating these transcription factor networks in each lung cancer subtype. Computational models are essential to fulfill this complex task and will help to analyze the multiple interactions within these networks, offering valuable insights that could improve clinical outcomes in lung cancer.

In this Special Issue, experts will highlight the role of transcription factors in lung cancer, deciphering the molecular mechanisms by which transcription factors promote NSCLC and SCLC and exploring their potential as therapeutic targets and biomarkers.

Dr. Kostas A. Papavassiliou
Prof. Dr. Athanasios G. Papavassiliou
Guest Editors

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Keywords

transcription factors
lung cancer
NSCLC SCLC
targeting
biomarkers
tumor suppressors
oncogenes
transcription factor network
computational models

Published Papers (4 papers)

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Editorial

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3 pages, 168 KiB

Open AccessEditorial

Immune Checkpoint Inhibitors in Non-Small Cell Lung Cancer (NSCLC) Treatment: Quo Vadis?

by Antonios N. Gargalionis, Kostas A. Papavassiliou and Athanasios G. Papavassiliou

Int. J. Mol. Sci. 2024, 25(12), 6309; https://doi.org/10.3390/ijms25126309 - 7 Jun 2024

Viewed by 331

Abstract

Lung cancer has been established as the second most common cancer worldwide (most common cancer in men and second most common cancer in women) and as the leading cause of cancer morbidity among neoplasms [...] Full article

(This article belongs to the Special Issue Transcription Factors in Lung Cancer: Mechanisms and Future Perspectives)

Research

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14 pages, 3305 KiB

Open AccessArticle

ADAMTS Gene-Derived circRNA Molecules in Non-Small-Cell Lung Cancer: Expression Profiling, Clinical Correlations and Survival Analysis

by Jacek Pietrzak, Rafał Świechowski, Agnieszka Wosiak, Szymon Wcisło and Ewa Balcerczak

Int. J. Mol. Sci. 2024, 25(3), 1897; https://doi.org/10.3390/ijms25031897 - 5 Feb 2024

Cited by 1 | Viewed by 1055

Abstract

The present study examines the relationship between circular RNA (circRNA) derived from three genes of the family a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTSs): ADAMTS6, ADAMTS9 and ADAMTS12 and the host gene expression in non-small-cell lung cancer (NSCLC) with regard to various clinical factors. Notably, an association was identified between ADAMTS12 expression and specific circRNA molecules, as well as certain expression patterns of ADAMTS6 and its derived circRNA that were specific to histopathological subtypes. The survival analysis demonstrated that a lower ADAMTS6 expression in squamous cell carcinoma was associated with extended survival. Furthermore, the higher ADAMTS9 expression was linked to prolonged survival, while the overexpression of ADAMTS12 was correlated with a shorter survival. These findings suggest that circRNA molecules may serve as potential diagnostic or prognostic biomarkers for NSCLC, highlighting the importance of considering molecular patterns in distinct cancer subtypes. Full article

(This article belongs to the Special Issue Transcription Factors in Lung Cancer: Mechanisms and Future Perspectives)

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21 pages, 4936 KiB

Open AccessArticle

BCL11A Expression in Non-Small Cell Lung Cancers

by Ewa Kątnik, Agnieszka Gomułkiewicz, Aleksandra Piotrowska, Jędrzej Grzegrzółka, Alicja Kmiecik, Katarzyna Ratajczak-Wielgomas, Anna Urbaniak, Natalia Glatzel-Plucińska, Piotr Błasiak and Piotr Dzięgiel

Int. J. Mol. Sci. 2023, 24(12), 9848; https://doi.org/10.3390/ijms24129848 - 7 Jun 2023

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Abstract

B-cell leukemia/lymphoma 11A (BCL11A) may be one of the potential biomarkers of non-small cell lung cancer (NSCLC). However, its role in the development of this cancer has not yet been precisely established. The aim of this study was to investigate the expression of BCL11A at the mRNA and protein levels in NSCLC cases and non-malignant lung tissue (NMLT) and to determine the relationship between BCL11A expression and the clinicopathological factors and Ki-67, Slug, Snail and Twist. The localization and the level of BCL11A protein were examined using immunohistochemistry (IHC) on 259 cases of NSCLC, and 116 NMLT samples were prepared as tissue microarrays and using immunofluorescence (IF) in the following cell lines: NCI-H1703, A549 and IMR-90. The mRNA expression of BCL11A was determined using real-time PCR in 33 NSCLC cases, 10 NMLT samples and the cell lines. BCL11A protein expression was significantly higher in NSCLC cases compared to NMLT. Nuclear expression was found in lung squamous cell carcinoma (SCC) cells, while cytoplasmic expression was demonstrated in adenocarcinoma (AC) cells. Nuclear expression of BCL11A decreased with increasing malignancy grade and correlated positively with Ki-67 and Slug and Twist expression. The opposite relationships were found for the cytoplasmic expression of BCL11A. Nuclear expression of BCL11A in NSCLC cells may affect tumor cell proliferation and change their phenotype, thus promoting tumor progression. Full article

(This article belongs to the Special Issue Transcription Factors in Lung Cancer: Mechanisms and Future Perspectives)

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11 pages, 1318 KiB

Open AccessArticle

Long-Lasting Therapeutic Response following Treatment with Pembrolizumab in Patients with Non-Small Cell Lung Cancer: A Real-World Experience

by Walid Shalata, Jeremy Zolnoorian, Gabrielle Migliozzi, Ashraf Abu Jama, Yulia Dudnik, Ahron Yehonatan Cohen, Amichay Meirovitz and Alexander Yakobson

Int. J. Mol. Sci. 2023, 24(6), 5938; https://doi.org/10.3390/ijms24065938 - 21 Mar 2023

Cited by 10 | Viewed by 3103

Abstract

Immune checkpoint inhibitors (ICIs), pembrolizumab in particular, have been shown to be vastly more efficacious than traditional cytotoxic or platinum-based chemotherapies in the treatment of non-small cell lung cancer (NSCLC). While there are plenty of data showing their efficacy and safety profiles, very little exists about the long-term effects of pembrolizumab. We compiled all patients with NSCLC who were treated with pembrolizumab at our institution and had progression-free survival (PFS) of at least 2 years during or after the treatment period. Within this group, we examined the long-term rates of PFS and overall survival (OS), side effect profiles, treatment, and overall disease course up to 60 months after starting treatment. This study included 36 patients with median (range) follow up times from treatment initiation in months as follows: 36 (28–65) overall; 39.5 (28–65) for adenocarcinoma; and 36 (30–58) for squamous cell carcinoma. The median (range) of OS and PFS (months) was comparable for adenocarcinoma, 36 (23–55); and squamous cell carcinoma, 35.5 (28–65). Overall, pembrolizumab shows remarkable long-term safety and efficacy in NSCLC patients. In patients who show an initially strong response and can make it to 24 months of PFS, disease progression after this period seems increasingly unlikely. Full article

(This article belongs to the Special Issue Transcription Factors in Lung Cancer: Mechanisms and Future Perspectives)

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Transcription Factors in Lung Cancer: Mechanisms and Future Perspectives

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