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Cancers
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Lung Cancer - Molecular Insights and Targeted Therapies
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Lung Cancer - Molecular Insights and Targeted Therapies

A special issue of Cancers (ISSN 2072-6694).

Deadline for manuscript submissions: closed (23 May 2023) | Viewed by 18136

Special Issue Editor

Dr. Sonia Molina-Pinelo

E-Mail Website
Guest Editor
Institute of Biomedicine of Seville (IBIS), HUVR, CSIC, Universidad de Sevilla, 41013 Sevilla, Spain
Interests: lung cancer; biomarkers; genetics; diagnosis; prognosis; targeted therapies; immunotherapy
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Lung cancer is the leading cause of cancer-related death worldwide, with a 5-year survival rate of approximately 18%. Each year, more than 2 million people are diagnosed with lung cancer around the world, and most of them are diagnosed with locally advanced or metastatic disease. Therefore, early diagnosis is one of the key steps to improve and promote precision medicine for this disease. 

Lung cancer management has changed in the last decade. The state-of-the-art molecular pathology has allowed the development of more effective therapeutic strategies for this disease. However, there is still a long way to go before precision medicine is available for all, which will require further research into the molecular mechanisms underlying lung cancer and potential new druggable targets based on the molecular background of tumors. The current issue aims to increase our knowledge in order to achieve these goals.

We are pleased to invite both original research and review articles that highlight recent advances in this exciting field of research. We are looking for articles focused on the discovery of molecular insights and targeted therapies for use in preclinical in vitro and in vivo models and/or articles investigating their role in translation to clinical practice. We also welcome articles that cover other topics with the aim of improving or providing an alternative paradigm of precision medicine in lung cancer.

I look forward to receiving your contributions. 

Dr. Sonia Molina-Pinelo
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. 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
  • non-small-cell lung cancer
  • small-cell lung cancer
  • biomarkers
  • oncogene-drive tumors
  • molecular mechanisms
  • targeted therapies
  • immunotherapy
  • precision medicine
  • preclinical models

Published Papers (7 papers)

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Research

Jump to: Review

23 pages, 5643 KiB  
Article
Aberrant Methylation of the Imprinted C19MC and MIR371-3 Clusters in Patients with Non-Small Cell Lung Cancer
by Laura Boyero, José Francisco Noguera-Uclés, Alejandro Castillo-Peña, Ana Salinas, Amparo Sánchez-Gastaldo, Miriam Alonso, Johana Cristina Benedetti, Reyes Bernabé-Caro, Luis Paz-Ares and Sonia Molina-Pinelo
Cancers 2023, 15(5), 1466; https://doi.org/10.3390/cancers15051466 - 25 Feb 2023
Cited by 1 | Viewed by 1867
Abstract
Epigenetic mechanisms have emerged as an important contributor to tumor development through the modulation of gene expression. Our objective was to identify the methylation profile of the imprinted C19MC and MIR371-3 clusters in patients with non-small cell lung cancer (NSCLC) and to find [...] Read more.
Epigenetic mechanisms have emerged as an important contributor to tumor development through the modulation of gene expression. Our objective was to identify the methylation profile of the imprinted C19MC and MIR371-3 clusters in patients with non-small cell lung cancer (NSCLC) and to find their potential target genes, as well as to study their prognostic role. DNA methylation status was analyzed in a NSCLC patient cohort (n = 47) and compared with a control cohort including COPD patients and non-COPD subjects (n = 23) using the Illumina Infinium Human Methylation 450 BeadChip. Hypomethylation of miRNAs located on chromosome 19q13.42 was found to be specific for tumor tissue. We then identified the target mRNA–miRNA regulatory network for the components of the C19MC and MIR371-3 clusters using the miRTargetLink 2.0 Human tool. The correlations of miRNA-target mRNA expression from primary lung tumors were analyzed using the CancerMIRNome tool. From those negative correlations identified, we found that a lower expression of 5 of the target genes (FOXF2, KLF13, MICA, TCEAL1 and TGFBR2) was significantly associated with poor overall survival. Taken together, this study demonstrates that the imprinted C19MC and MIR371-3 miRNA clusters undergo polycistronic epigenetic regulation leading to deregulation of important and common target genes with potential prognostic value in lung cancer. Full article
(This article belongs to the Special Issue Lung Cancer - Molecular Insights and Targeted Therapies)
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18 pages, 8566 KiB  
Article
Antigene MYCN Silencing by BGA002 Inhibits SCLC Progression Blocking mTOR Pathway and Overcomes Multidrug Resistance
by Sonia Bortolotti, Silvia Angelucci, Luca Montemurro, Damiano Bartolucci, Salvatore Raieli, Silvia Lampis, Camilla Amadesi, Annalisa Scardovi, Giammario Nieddu, Lucia Cerisoli, Francesca Paganelli, Francesca Chiarini, Gabriella Teti, Mirella Falconi, Andrea Pession, Patrizia Hrelia and Roberto Tonelli
Cancers 2023, 15(3), 990; https://doi.org/10.3390/cancers15030990 - 03 Feb 2023
Cited by 2 | Viewed by 2325
Abstract
Small-cell lung cancer (SCLC) is the most aggressive lung cancer type, and is associated with smoking, low survival rate due to high vascularization, metastasis and drug resistance. Alterations in MYC family members are biomarkers of poor prognosis for a large number of SCLC. [...] Read more.
Small-cell lung cancer (SCLC) is the most aggressive lung cancer type, and is associated with smoking, low survival rate due to high vascularization, metastasis and drug resistance. Alterations in MYC family members are biomarkers of poor prognosis for a large number of SCLC. In particular, MYCN alterations define SCLC cases with immunotherapy failure. MYCN has a highly restricted pattern of expression in normal cells and is an ideal target for cancer therapy but is undruggable by traditional approaches. We propose an innovative approach to MYCN inhibition by an MYCN-specific antigene—PNA oligonucleotide (BGA002)—as a new precision medicine for MYCN-related SCLC. We found that BGA002 profoundly and specifically inhibited MYCN expression in SCLC cells, leading to cell-growth inhibition and apoptosis, while also overcoming multidrug resistance. These effects are driven by mTOR pathway block in concomitance with autophagy reactivation, thus avoiding the side effects of targeting mTOR in healthy cells. Moreover, we identified an MYCN-related SCLC gene signature comprehending CNTFR, DLX5 and TNFAIP3, that was reverted by BGA002. Finally, systemic treatment with BGA002 significantly increased survival in MYCN-amplified SCLC mouse models, including in a multidrug-resistant model in which tumor vascularization was also eliminated. These findings warrant the clinical testing of BGA002 in MYCN-related SCLC. Full article
(This article belongs to the Special Issue Lung Cancer - Molecular Insights and Targeted Therapies)
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14 pages, 4404 KiB  
Communication
Both In Situ and Circulating SLC3A2 Could Be Used as Prognostic Markers for Human Lung Squamous Cell Carcinoma and Lung Adenocarcinoma
by Dahua Liu, Min An, Guimin Wen, Yanan Xing and Pu Xia
Cancers 2022, 14(21), 5191; https://doi.org/10.3390/cancers14215191 - 22 Oct 2022
Cited by 3 | Viewed by 1471
Abstract
SLC3A2, the heavy chain of the CD98 protein, is highly expressed in many cancers, including lung cancer. It can regulate the proliferation and the metastasis of cancer cells via the integrin signaling pathway. Liquid biopsy is a novel method for tumor diagnosis. The [...] Read more.
SLC3A2, the heavy chain of the CD98 protein, is highly expressed in many cancers, including lung cancer. It can regulate the proliferation and the metastasis of cancer cells via the integrin signaling pathway. Liquid biopsy is a novel method for tumor diagnosis. The diagnostic or prognostic roles of serum SLC3A2 in lung cancer are still not clear. In this study, we analyzed SLC3A2 mRNA levels in human lung squamous cell carcinoma (LUSC) and lung adenocarcinoma (LUAD) using the TCGA database and serum SLC3A2 protein levels using ELISA. We confirmed high SLC3A2 levels in both the serum and tissue of LUAD and LUSC patients. Both serum and tissue SLC3A2 could be used as prognostic markers for overall LUAD and subgroups of LUSC patients. SLC3A2 induced tumorigenesis via the MEK/ERK signaling pathway in LUAD and LUSC cells. Full article
(This article belongs to the Special Issue Lung Cancer - Molecular Insights and Targeted Therapies)
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19 pages, 4475 KiB  
Article
Virtual Screening and Quantitative Structure–Activity Relationship of Moringa oleifera with Melanoma Antigen A (MAGE-A) Genes against the Therapeutics of Non-Small Cell Lung Cancers (NSCLCs)
by Smitha S. Bhat, Shreya Das Mahapatra, Sindhu R, Sarana Rose Sommano and Shashanka K. Prasad
Cancers 2022, 14(20), 5052; https://doi.org/10.3390/cancers14205052 - 15 Oct 2022
Cited by 2 | Viewed by 1810
Abstract
In the last decade, there have been significant advancements in the treatment of non-small cell lung cancer, including remarkable gains in detection, diagnosis, and therapy. The emergence of molecular targeted therapies, immunotherapeutic inhibitors, and antiangiogenesis medicines has largely fueled improvements in combination therapy [...] Read more.
In the last decade, there have been significant advancements in the treatment of non-small cell lung cancer, including remarkable gains in detection, diagnosis, and therapy. The emergence of molecular targeted therapies, immunotherapeutic inhibitors, and antiangiogenesis medicines has largely fueled improvements in combination therapy and systemic treatments, all of which have dramatically ameliorated patient outcomes. The Moringa oleifera bioactive compounds have been effective in the suppression of cancers, making them the therapeutic agents of choice for the current investigation to treat MAGE-A presented in NSCLC. The ligand entrants were screened for their pharmacological properties, and 2,2-diphenyl-1,3-benzodioxole was stipulated as the lead candidate. 2,2-Diphenyl-1,3-benzodioxole exhibited better pharmacological properties and superior binding with branched-chain amino acids, making it an ideal candidate to address MAGE-A. The study concluded that addressing MAGE-A to impede their activity and antigenicity can be exploited as immunotarget(s). Full article
(This article belongs to the Special Issue Lung Cancer - Molecular Insights and Targeted Therapies)
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14 pages, 1825 KiB  
Article
The High Proportion of Discordant EGFR Mutations among Multiple Lung Tumors
by Hyunwoo Lee, Jin Hee Park, Joungho Han, Young Mog Shim, Jhingook Kim, Yong Soo Choi, Hong Kwan Kim, Jong Ho Cho, Yoon-La Choi and Wan-Seop Kim
Cancers 2022, 14(12), 3011; https://doi.org/10.3390/cancers14123011 - 18 Jun 2022
Cited by 1 | Viewed by 1715
Abstract
The prevalence of multiple lung cancers has been increasing recently. Molecular analysis of epidermal growth factor receptor (EGFR) mutations in individual tumors of multiple lung cancers is essential for devising an optimal therapeutic strategy. The EGFR mutation status in multiple lung [...] Read more.
The prevalence of multiple lung cancers has been increasing recently. Molecular analysis of epidermal growth factor receptor (EGFR) mutations in individual tumors of multiple lung cancers is essential for devising an optimal therapeutic strategy. The EGFR mutation status in multiple lung cancers was evaluated to determine its therapeutic implications. In total, 208 tumors from 101 patients who underwent surgery for multiple lung cancers were analyzed. Individual tumors were subjected to histological evaluation and EGFR analysis using a real-time polymerase chain reaction. Additionally, EGFR-wildtype tumors were subjected to next-generation sequencing (NGS). EGFR mutations were detected in 113 tumors from 72 patients, predominantly in females (p < 0.001) and non-smokers (p < 0.001). Among patients with at least one EGFR-mutant tumor, approximately 72% of patients (52/72) had different EGFR mutations in individual tumors. NGS analysis of EGFR-wildtype tumors from 12 patients revealed four and eight cases with concordant and discordant molecular alterations, respectively. These findings revealed a high proportion of discordant EGFR mutations among multiple lung tumors. Hence, EGFR analysis of individual tumors of multiple lung tumors is essential for the evaluation of clonality and the development of an optimal treatment strategy. Full article
(This article belongs to the Special Issue Lung Cancer - Molecular Insights and Targeted Therapies)
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Review

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21 pages, 7124 KiB  
Review
Novel Targets, Novel Treatments: The Changing Landscape of Non-Small Cell Lung Cancer
by Dorine de Jong, Jeeban P. Das, Hong Ma, Jacienta Pailey Valiplackal, Conor Prendergast, Tina Roa, Brian Braumuller, Aileen Deng, Laurent Dercle, Randy Yeh, Mary M. Salvatore and Kathleen M. Capaccione
Cancers 2023, 15(10), 2855; https://doi.org/10.3390/cancers15102855 - 21 May 2023
Cited by 5 | Viewed by 3269
Abstract
Treatment of non-small cell lung cancer (NSCLC) has undergone a paradigm shift. Once a disease with limited potential therapies, treatment options for patients have exploded with the availability of molecular testing to direct management and targeted therapies to treat tumors with specific driver [...] Read more.
Treatment of non-small cell lung cancer (NSCLC) has undergone a paradigm shift. Once a disease with limited potential therapies, treatment options for patients have exploded with the availability of molecular testing to direct management and targeted therapies to treat tumors with specific driver mutations. New in vitro diagnostics allow for the early and non-invasive detection of disease, and emerging in vivo imaging techniques allow for better detection and monitoring. The development of checkpoint inhibitor immunotherapy has arguably been the biggest advance in lung cancer treatment, given that the vast majority of NSCLC tumors can be treated with these therapies. Specific targeted therapies, including those against KRAS, EGFR, RTK, and others have also improved the outcomes for those individuals bearing an actionable mutation. New and emerging therapies, such as bispecific antibodies, CAR T cell therapy, and molecular targeted radiotherapy, offer promise to patients for whom none of the existing therapies have proved effective. In this review, we provide the most up-to-date survey to our knowledge regarding emerging diagnostic and therapeutic strategies for lung cancer to provide clinicians with a comprehensive reference of the options for treatment available now and those which are soon to come. Full article
(This article belongs to the Special Issue Lung Cancer - Molecular Insights and Targeted Therapies)
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25 pages, 1287 KiB  
Review
Treatment Strategies for Non-Small Cell Lung Cancer with Common EGFR Mutations: A Review of the History of EGFR TKIs Approval and Emerging Data
by Julian A. Marin-Acevedo, Bruna Pellini, ErinMarie O. Kimbrough, J. Kevin Hicks and Alberto Chiappori
Cancers 2023, 15(3), 629; https://doi.org/10.3390/cancers15030629 - 19 Jan 2023
Cited by 8 | Viewed by 4746
Abstract
The development of targeted therapies over the past two decades has led to a dramatic change in the management of EGFR-mutant non-small cell lung cancer (NSCLC). While there are currently five approved EGFR tyrosine kinase inhibitors (TKIs) for treating EGFR-mutant NSCLC [...] Read more.
The development of targeted therapies over the past two decades has led to a dramatic change in the management of EGFR-mutant non-small cell lung cancer (NSCLC). While there are currently five approved EGFR tyrosine kinase inhibitors (TKIs) for treating EGFR-mutant NSCLC in the first-line setting, therapy selection after progression on EGFR TKIs remains complex. Multiple groups are investigating novel therapies and drug combinations to determine the optimal therapy and treatment sequence for these patients. In this review, we summarize the landmark trials and history of the approval of EGFR TKIs, their efficacy and tolerability, and the role of these therapies in patients with central nervous system metastasis. We also briefly discuss the mechanisms of resistance to EGFR TKIs, ongoing attempts to overcome resistance and improve outcomes, and finalize by offering treatment sequencing recommendations. Full article
(This article belongs to the Special Issue Lung Cancer - Molecular Insights and Targeted Therapies)
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