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Molecular Research on Non-small Cell Lung Cancer (NSCLC) Therapy

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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: closed (25 February 2024) | Viewed by 4515

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Special Issue Editor

Dr. Margarita Pustovalova

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Guest Editor

Moscow Institute of Physics and Technology, 9 Institutskiy per., Dolgoprudny, 141700 Moscow, Russia
Interests: oncology; non-small cell lung cancer; DNA damage and repair; ionizing radiation; cancer stem cells; radioresistance; polyploid / multinucleated giant cancer cells

Special Issue Information

Dear Colleagues,

Lung cancer is the leading cause of cancer-related deaths worldwide. Non-small cell lung cancer (NSCLC) represents ~85% of all lung cancer cases. Treatment choices for NSCLC include surgery, chemotherapy, radiation therapy, targeted therapy, and immunotherapy. However, therapy resistance is still a major clinical problem, leading to poor prognosis of patients with NSCLC. Therapy resistance is linked to both intrinsic (cancer stem cells, polyploid/multinucleated giant cancer cells, mutational status, epithelial–mesenchymal transition (EMT) process) and extrinsic (hypoxia, tumor microenvironment, immune response) mechanisms in which cancer cells accumulate genetic and molecular changes, allowing them to survive treatment conditions and repopulate. In this case, understanding the genetic alterations and signal molecular pathways in NSCLC cells’ therapy resistance is important for the selection of new therapeutic approaches that improve clinical outcome and survival for NSCLC patients.

This Special Issue focuses on “Molecular Research on Non-small Cell Lung Cancer (NSCLC) Therapy”. Review manuscripts as well as original studies demonstrating novel therapeutic targets of NSCLC as well as new approaches for overcoming NSCLC therapy resistance will be considered for publication.

Dr. Margarita Pustovalova
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 short 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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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

non-small cell lung cancer
radioresistance
gene expression
signaling pathways

Published Papers (3 papers)

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Research

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23 pages, 4665 KiB

Open AccessArticle

Loss of Key EMT-Regulating miRNAs Highlight the Role of ZEB1 in EGFR Tyrosine Kinase Inhibitor-Resistant NSCLC

by Linus Gohlke, Ahmad Alahdab, Angela Oberhofer, Karolina Worf, Stefan Holdenrieder, Martin Michaelis, Jindrich Cinatl, Jr. and Christoph A Ritter

Int. J. Mol. Sci. 2023, 24(19), 14742; https://doi.org/10.3390/ijms241914742 - 29 Sep 2023

Cited by 3 | Viewed by 1424

Abstract

Despite recent advances in the treatment of non-small cell lung cancer (NSCLC), acquired drug resistance to targeted therapy remains a major obstacle. Epithelial-mesenchymal transition (EMT) has been identified as a key resistance mechanism in NSCLC. Here, we investigated the mechanistic role of key EMT-regulating small non-coding microRNAs (miRNAs) in sublines of the NSCLC cell line HCC4006 adapted to afatinib, erlotinib, gefitinib, or osimertinib. The most differentially expressed miRNAs derived from extracellular vesicles were associated with EMT, and their predicted target ZEB1 was significantly overexpressed in all resistant cell lines. Transfection of a miR-205-5p mimic partially reversed EMT by inhibiting ZEB1, restoring CDH1 expression, and inhibiting migration in erlotinib-resistant cells. Gene expression of EMT-markers, transcription factors, and miRNAs were correlated during stepwise osimertinib adaptation of HCC4006 cells. Temporally relieving cells of osimertinib reversed transition trends, suggesting that the implementation of treatment pauses could provide prolonged benefits for patients. Our results provide new insights into the contribution of miRNAs to drug-resistant NSCLC harboring EGFR-activating mutations and highlight their role as potential biomarkers and therapeutic targets. Full article

(This article belongs to the Special Issue Molecular Research on Non-small Cell Lung Cancer (NSCLC) Therapy)

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13 pages, 1886 KiB

Open AccessArticle

THSD7A Positivity Predicts Poor Survival and Is Linked to High FAK Expression and FGFR1-Wildtype in Female Patients with Squamous Cell Carcinoma of the Lung

by Fidelis Andrea Flockerzi, Johannes Hohneck, Frank Langer, Rainer Maria Bohle and Phillip Rolf Stahl

Int. J. Mol. Sci. 2023, 24(13), 10639; https://doi.org/10.3390/ijms241310639 - 26 Jun 2023

Cited by 1 | Viewed by 1029

Abstract

Lung cancer is the leading cause of cancer-related deaths in the western world, with squamous cell carcinoma being one of the most common histological subtypes. Prognostic and predictive markers are still largely missing for squamous cell carcinoma of the lung (LSCC). Several studies indicate that THSD7A might at least play a role in the prognosis of different tumors. FAK seems to play an important role in lung cancer and is discussed as a potential therapeutic target. In addition, there is evidence that FAK-dependent signaling pathways might be affected by THSD7A. For that reason, we investigated the role of THSD7A as a potential tumor marker in LSCC and whether THSD7A expression has an impact on the expression level of FAK. A total of 101 LSCCs were analyzed by immunohistochemistry using tissue microarrays. THSD7A positivity was associated with poor overall survival in female patients and showed a relation to high FAK expression in this subgroup. To our knowledge, we are the first to report these correlations in lung cancer. The results might be proof of the assumed activation of FAK-dependent signaling pathways by THSD7A and that as a membrane-associated protein, THSD7A might serve as a putative therapeutic target in LSCC. Full article

(This article belongs to the Special Issue Molecular Research on Non-small Cell Lung Cancer (NSCLC) Therapy)

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Review

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23 pages, 1439 KiB

Open AccessReview

Exploring the Molecular Tumor Microenvironment and Translational Biomarkers in Brain Metastases of Non-Small-Cell Lung Cancer

by Jiexi Wen, Jie-Zeng Yu, Catherine Liu, A. Aziz O. Ould Ismail and Weijie Ma

Int. J. Mol. Sci. 2024, 25(4), 2044; https://doi.org/10.3390/ijms25042044 - 7 Feb 2024

Cited by 1 | Viewed by 1554

Abstract

Brain metastases represent a significant clinical challenge in the treatment of non-small-cell lung cancer (NSCLC), often leading to a severe decline in patient prognosis and survival. Recent advances in imaging and systemic treatments have increased the detection rates of brain metastases, yet clinical outcomes remain dismal due to the complexity of the metastatic tumor microenvironment (TME) and the lack of specific biomarkers for early detection and targeted therapy. The intricate interplay between NSCLC tumor cells and the surrounding TME in brain metastases is pivotal, influencing tumor progression, immune evasion, and response to therapy. This underscores the necessity for a deeper understanding of the molecular underpinnings of brain metastases, tumor microenvironment, and the identification of actionable biomarkers that can inform multimodal treatment approaches. The goal of this review is to synthesize current insights into the TME and elucidate molecular mechanisms in NSCLC brain metastases. Furthermore, we will explore the promising horizon of emerging biomarkers, both tissue- and liquid-based, that hold the potential to radically transform the treatment strategies and the enhancement of patient outcomes. Full article

(This article belongs to the Special Issue Molecular Research on Non-small Cell Lung Cancer (NSCLC) Therapy)

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