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Towards New Promising Discoveries for Lung Cancer Patients: A Selection...
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Towards New Promising Discoveries for Lung Cancer Patients: A Selection of Papers from the First Joint Meeting on Lung Cancer of the FHU OncoAge (Nice, France) and the MD Anderson Cancer Center (Houston, TX, USA)

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

Deadline for manuscript submissions: closed (31 January 2019) | Viewed by 82375

Printed Edition Available!
A printed edition of this Special Issue is available here.

Special Issue Editors

Prof. Dr. George A. Calin

grade E-Mail Website
Guest Editor
Department of Translational Molecular Pathology, Center for RNA Interference and Non-Coding RNAs, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Interests: non-coding RNA; microRNA; cancer; metastasis
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Paul Hofman

E-Mail Website
Guest Editor
FHU OncoAge, IHU RespirERA, University Côte d’Azur, Nice, France
Interests: predictive biomarkers in lung cancer; liquid biopsy; molecular biology; artificial intelligence
Special Issues, Collections and Topics in MDPI journals
Dr. Sendurai A. Mani

E-Mail Website
Guest Editor
Department of Translational Molecular Pathology, Metastasis Research Center, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Interests: EMT; cancer stem cells
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

This Special Issue of Cancers will consist of selected papers from the First Annual Joint Meeting on Lung Cancer of the FHU OncoAge (www.oncoage.org, University of Côte d’Azur) and the MD Anderson Cancer Center (MDACC, University of Texas, Houston, USA), taking place in Nice (France), on 6–7 September, 2018. The FHU OncoAge was established in 2015 to bring together scientists and physicians with a shared interest in aging-related cancers, in particular, lung cancer, but also thoracic pre-neoplastic diseases, such as Chronic Obstructive Pulmonary Disease (COPD) and Idiopathic Pulmonary Fibrosis (IPF), and to provide a platform for improving research, patients health care and training for fighting age-related pathologies. In this context, a partnership with research groups, scientists and physicians between FHU OncoAge and the MD Anderson Cancer Center has been created to work in the context of age-related lung cancer and non-tumor lung diseases because both age-related chronic diseases and cancer share genomic, immune, metabolic and other biological abnormalities. Moreover, theses lung pathologies associate similar conditions inducing cellular senescence, genomic instability, oxidative stress, DNA damage, dysfunction of mitochondria, etc. Moreover, deciphering the clinical features, the biological markers, the environmental factors that are shared between chronic age-related lung pathologies and lung cancers will lead to the development of rational new clinical practices, including the validation of surrogate biomarkers of predictive response to new therapies, but also the validation of active preventive strategies. The cooperation between the FHU OncoAge and the MDACC will ensure the implementation of innovative projects. This international conference represents a major event for the medical and scientific community working on lung cancer and promises to be an inspiring meeting. Particular attention will be given to new advances in biomarker development and novel therapeutic strategies for new pathophysiological concepts.

This Special Issue will cover new and novel areas of research pertaining to lung cancer presented in this two-day conference. This issue will represent state-of-the-art and up-to-date coverage of progress dedicated to the pathology of lung cancer.

Prof. Dr. Georges A Calin
Prof. Dr. Paul Hofman
Dr. Sendurai A. Mani
Guest Editors

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.

Published Papers (13 papers)

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Research

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18 pages, 2914 KiB  
Article
Ntrk1 Promotes Resistance to PD-1 Checkpoint Blockade in Mesenchymal Kras/p53 Mutant Lung Cancer
by Jessica M. Konen, B. Leticia Rodriguez, Jared J. Fradette, Laura Gibson, Denali Davis, Rosalba Minelli, Michael D. Peoples, Jeffrey Kovacs, Alessandro Carugo, Christopher Bristow, Timothy Heffernan and Don L. Gibbons
Cancers 2019, 11(4), 462; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers11040462 - 02 Apr 2019
Cited by 19 | Viewed by 6704
Abstract
The implementation of cancer immunotherapeutics for solid tumors including lung cancers has improved clinical outcomes in a small percentage of patients. However, the majority of patients show little to no response or acquire resistance during treatment with checkpoint inhibitors delivered as a monotherapy. [...] Read more.
The implementation of cancer immunotherapeutics for solid tumors including lung cancers has improved clinical outcomes in a small percentage of patients. However, the majority of patients show little to no response or acquire resistance during treatment with checkpoint inhibitors delivered as a monotherapy. Therefore, identifying resistance mechanisms and novel combination therapy approaches is imperative to improve responses to immune checkpoint inhibitors. To address this, we performed an in vivo shRNA dropout screen that focused on genes encoding for FDA-approved drug targets (FDAome). We implanted epithelial and mesenchymal Kras/p53 (KP) mutant murine lung cancer cells expressing the FDAome shRNA library into syngeneic mice treated with an anti-PD-1 antibody. Sequencing for the barcoded shRNAs revealed Ntrk1 was significantly depleted from mesenchymal tumors challenged with PD-1 blockade, suggesting it provides a survival advantage to tumor cells when under immune system pressure. Our data confirmed Ntrk1 transcript levels are upregulated in tumors treated with PD-1 inhibitors. Additionally, analysis of tumor-infiltrating T cell populations revealed that Ntrk1 can promote CD8+ T cell exhaustion. Lastly, we found that Ntrk1 regulates Jak/Stat signaling to promote expression of PD-L1 on tumor cells. Together, these data suggest that Ntrk1 activates Jak/Stat signaling to regulate expression of immunosuppressive molecules including PD-L1, promoting exhaustion within the tumor microenvironment. Full article
(This article belongs to the Special Issue Towards New Promising Discoveries for Lung Cancer Patients: A Selection of Papers from the First Joint Meeting on Lung Cancer of the FHU OncoAge (Nice, France) and the MD Anderson Cancer Center (Houston, TX, USA))
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11 pages, 268 KiB  
Article
The Desire to Better Understand Older Adults with Solid Tumors to Improve Management: Assessment and Guided Interventions—The French PACA EST Cohort Experience
by Rabia Boulahssass, Sebastien Gonfrier, Noémie Champigny, Sandra Lassalle, Eric François, Paul Hofman and Olivier Guerin
Cancers 2019, 11(2), 192; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers11020192 - 07 Feb 2019
Cited by 9 | Viewed by 2822
Abstract
Todays challenge in geriatric oncology is to screen patients who need geriatric follow-up. The main goal of this study was to analyze factors that identify patients, in a large cohort of patients with solid tumors, who need more geriatric interventions and therefore specific [...] Read more.
Todays challenge in geriatric oncology is to screen patients who need geriatric follow-up. The main goal of this study was to analyze factors that identify patients, in a large cohort of patients with solid tumors, who need more geriatric interventions and therefore specific follow-up. Between April 2012 and May 2018, 3530 consecutive patients were enrolled in the PACA EST cohort (France). A total of 3140 patients were finally enrolled in the study. A Comprehensive Geriatric Assessment (CGA) was performed at baseline. We analyzed the associations between factors at baseline (geriatric and oncologic factors) and the need to perform more than three geriatric interventions. The mean age of the population was 82 years old with 59% of patients aged older than 80 years old. A total of 8819 geriatric interventions were implemented for the 3140 patients. The percentage of patients with three or more geriatric interventions represented 31.8% (n = 999) of the population. In multivariate analyses, a Mini Nutritional assessment (MNA) <17, an MNA ≤23·5 and ≥17, a performans status (PS) >2, a dependence on Instrumental Activities of Daily Living (IADL), a Geriatric Depression Scale (GDS) ≥5, a Mini Mental State Examination (MMSE) <24, and a Screening tool G8 ≤14 were independent risk factors associated with more geriatric interventions. Factors associated with more geriatric interventions could assist practitioners in selecting patients for specific geriatric follow-up. Full article
(This article belongs to the Special Issue Towards New Promising Discoveries for Lung Cancer Patients: A Selection of Papers from the First Joint Meeting on Lung Cancer of the FHU OncoAge (Nice, France) and the MD Anderson Cancer Center (Houston, TX, USA))

Review

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17 pages, 674 KiB  
Review
Targeting the Interplay between Epithelial-to-Mesenchymal-Transition and the Immune System for Effective Immunotherapy
by Rama Soundararajan, Jared J. Fradette, Jessica M. Konen, Stacy Moulder, Xiang Zhang, Don L. Gibbons, Navin Varadarajan, Ignacio I. Wistuba, Debasish Tripathy, Chantale Bernatchez, Lauren A. Byers, Jeffrey T. Chang, Alejandro Contreras, Bora Lim, Edwin Roger Parra, Emily B. Roarty, Jing Wang, Fei Yang, Michelle Barton, Jeffrey M. Rosen and Sendurai A. Maniadd Show full author list remove Hide full author list
Cancers 2019, 11(5), 714; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers11050714 - 24 May 2019
Cited by 83 | Viewed by 6416
Abstract
Over the last decade, both early diagnosis and targeted therapy have improved the survival rates of many cancer patients. Most recently, immunotherapy has revolutionized the treatment options for cancers such as melanoma. Unfortunately, a significant portion of cancers (including lung and breast cancers) [...] Read more.
Over the last decade, both early diagnosis and targeted therapy have improved the survival rates of many cancer patients. Most recently, immunotherapy has revolutionized the treatment options for cancers such as melanoma. Unfortunately, a significant portion of cancers (including lung and breast cancers) do not respond to immunotherapy, and many of them develop resistance to chemotherapy. Molecular characterization of non-responsive cancers suggest that an embryonic program known as epithelial-mesenchymal transition (EMT), which is mostly latent in adults, can be activated under selective pressures, rendering these cancers resistant to chemo- and immunotherapies. EMT can also drive tumor metastases, which in turn also suppress the cancer-fighting activity of cytotoxic T cells that traffic into the tumor, causing immunotherapy to fail. In this review, we compare and contrast immunotherapy treatment options of non-small cell lung cancer (NSCLC) and triple negative breast cancer (TNBC). We discuss why, despite breakthrough progress in immunotherapy, attaining predictable outcomes in the clinic is mostly an unsolved problem for these tumors. Although these two cancer types appear different based upon their tissues of origin and molecular classification, gene expression indicate that they possess many similarities. Patient tumors exhibit activation of EMT, and resulting stem cell properties in both these cancer types associate with metastasis and resistance to existing cancer therapies. In addition, the EMT transition in both these cancers plays a crucial role in immunosuppression, which exacerbates treatment resistance. To improve cancer-related survival we need to understand and circumvent, the mechanisms through which these tumors become therapy resistant. In this review, we discuss new information and complementary perspectives to inform combination treatment strategies to expand and improve the anti-tumor responses of currently available clinical immune checkpoint inhibitors. Full article
(This article belongs to the Special Issue Towards New Promising Discoveries for Lung Cancer Patients: A Selection of Papers from the First Joint Meeting on Lung Cancer of the FHU OncoAge (Nice, France) and the MD Anderson Cancer Center (Houston, TX, USA))
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12 pages, 688 KiB  
Review
MicroRNAs and Long Non-Coding RNAs and Their Hormone-Like Activities in Cancer
by Barbara Pardini and George A. Calin
Cancers 2019, 11(3), 378; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers11030378 - 17 Mar 2019
Cited by 39 | Viewed by 3758
Abstract
Hormones are messengers circulating in the body that interact with specific receptors on the cell membrane or inside the cells and regulate, at a distal site, the activities of specific target organs. The definition of hormone has evolved in the last years. Hormones [...] Read more.
Hormones are messengers circulating in the body that interact with specific receptors on the cell membrane or inside the cells and regulate, at a distal site, the activities of specific target organs. The definition of hormone has evolved in the last years. Hormones are considered in the context of cell–cell communication and mechanisms of cellular signaling. The best-known mechanisms of this kind are chemical receptor-mediated events, the cell–cell direct interactions through synapses, and, more recently, the extracellular vesicle (EV) transfer between cells. Recently, it has been extensively demonstrated that EVs are used as a way of communication between cells and that they are transporters of specific messenger signals including non-coding RNAs (ncRNAs) such as microRNAs (miRNAs) and long non-coding RNAs (lncRNAs). Circulating ncRNAs in body fluids and extracellular fluid compartments may have endocrine hormone-like effects because they can act at a distance from secreting cells with widespread consequences within the recipient cells. Here, we discuss and report examples of the potential role of miRNAs and lncRNAs as mediator for intercellular communication with a hormone-like mechanism in cancer. Full article
(This article belongs to the Special Issue Towards New Promising Discoveries for Lung Cancer Patients: A Selection of Papers from the First Joint Meeting on Lung Cancer of the FHU OncoAge (Nice, France) and the MD Anderson Cancer Center (Houston, TX, USA))
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29 pages, 1925 KiB  
Review
Macrophage Origin, Metabolic Reprogramming and IL-1β Signaling: Promises and Pitfalls in Lung Cancer
by Emma Guilbaud, Emmanuel L. Gautier and Laurent Yvan-Charvet
Cancers 2019, 11(3), 298; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers11030298 - 02 Mar 2019
Cited by 13 | Viewed by 6950
Abstract
Macrophages are tissue-resident cells that act as immune sentinels to maintain tissue integrity, preserve self-tolerance and protect against invading pathogens. Lung macrophages within the distal airways face around 8000–9000 L of air every day and for that reason are continuously exposed to a [...] Read more.
Macrophages are tissue-resident cells that act as immune sentinels to maintain tissue integrity, preserve self-tolerance and protect against invading pathogens. Lung macrophages within the distal airways face around 8000–9000 L of air every day and for that reason are continuously exposed to a variety of inhaled particles, allergens or airborne microbes. Chronic exposure to irritant particles can prime macrophages to mediate a smoldering inflammatory response creating a mutagenic environment and favoring cancer initiation. Tumor-associated macrophages (TAMs) represent the majority of the tumor stroma and maintain intricate interactions with malignant cells within the tumor microenvironment (TME) largely influencing the outcome of cancer growth and metastasis. A number of macrophage-centered approaches have been investigated as potential cancer therapy and include strategies to limit their infiltration or exploit their antitumor effector functions. Recently, strategies aimed at targeting IL-1β signaling pathway using a blocking antibody have unexpectedly shown great promise on incident lung cancer. Here, we review the current understanding of the bridge between TAM metabolism, IL-1β signaling, and effector functions in lung adenocarcinoma and address the challenges to successfully incorporating these pathways into current anticancer regimens. Full article
(This article belongs to the Special Issue Towards New Promising Discoveries for Lung Cancer Patients: A Selection of Papers from the First Joint Meeting on Lung Cancer of the FHU OncoAge (Nice, France) and the MD Anderson Cancer Center (Houston, TX, USA))
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22 pages, 8621 KiB  
Review
Multiplexed Immunohistochemistry for Molecular and Immune Profiling in Lung Cancer—Just About Ready for Prime-Time?
by Paul Hofman, Cécile Badoual, Fiona Henderson, Léa Berland, Marame Hamila, Elodie Long-Mira, Sandra Lassalle, Hélène Roussel, Véronique Hofman, Eric Tartour and Marius Ilié
Cancers 2019, 11(3), 283; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers11030283 - 27 Feb 2019
Cited by 84 | Viewed by 10679
Abstract
As targeted molecular therapies and immuno-oncology have become pivotal in the management of patients with lung cancer, the essential requirement for high throughput analyses and clinical validation of biomarkers has become even more intense, with response rates maintained in the 20%–30% range. Moreover, [...] Read more.
As targeted molecular therapies and immuno-oncology have become pivotal in the management of patients with lung cancer, the essential requirement for high throughput analyses and clinical validation of biomarkers has become even more intense, with response rates maintained in the 20%–30% range. Moreover, the list of treatment alternatives, including combination therapies, is rapidly evolving. The molecular profiling and specific tumor-associated immune contexture may be predictive of response or resistance to these therapeutic strategies. Multiplexed immunohistochemistry is an effective and proficient approach to simultaneously identify specific proteins or molecular abnormalities, to determine the spatial distribution and activation state of immune cells, as well as the presence of immunoactive molecular expression. This method is highly advantageous for investigating immune evasion mechanisms and discovering potential biomarkers to assess mechanisms of action and to predict response to a given treatment. This review provides views on the current technological status and evidence for clinical applications of multiplexing and how it could be applied to optimize clinical management of patients with lung cancer. Full article
(This article belongs to the Special Issue Towards New Promising Discoveries for Lung Cancer Patients: A Selection of Papers from the First Joint Meeting on Lung Cancer of the FHU OncoAge (Nice, France) and the MD Anderson Cancer Center (Houston, TX, USA))
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14 pages, 602 KiB  
Review
Circulating Tumor Cell Detection in Lung Cancer: But to What End?
by Véronique Hofman, Simon Heeke, Charles-Hugo Marquette, Marius Ilié and Paul Hofman
Cancers 2019, 11(2), 262; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers11020262 - 23 Feb 2019
Cited by 17 | Viewed by 4468
Abstract
The understanding of the natural history and biology of lung cancer has been enhanced by studies into circulating tumor cells (CTCs). Fundamental and translational research, as well as clinical trials in the characterization and behavior of these cells, have constantly contributed to improving [...] Read more.
The understanding of the natural history and biology of lung cancer has been enhanced by studies into circulating tumor cells (CTCs). Fundamental and translational research, as well as clinical trials in the characterization and behavior of these cells, have constantly contributed to improving understanding within the domain of thoracic oncology. However, the use of these CTCs as prognostic and predictive biomarkers has not been adopted to the same extent as circulating free DNA (cf-DNA) in plasma, in the daily practice of thoracic oncologists. However, recent technological advances have firmly put the detection and characterization of CTCs in thoracic oncology back on the agenda, and have opened up perspectives for their routine clinical use. This review discusses the major advances of using CTCs in the domain of thoracic oncology, as well as the envisaged short- and long-term prospects. Full article
(This article belongs to the Special Issue Towards New Promising Discoveries for Lung Cancer Patients: A Selection of Papers from the First Joint Meeting on Lung Cancer of the FHU OncoAge (Nice, France) and the MD Anderson Cancer Center (Houston, TX, USA))
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23 pages, 15676 KiB  
Review
State-of-the-Art of Profiling Immune Contexture in the Era of Multiplexed Staining and Digital Analysis to Study Paraffin Tumor Tissues
by Edwin Roger Parra, Alejandro Francisco-Cruz and Ignacio Ivan Wistuba
Cancers 2019, 11(2), 247; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers11020247 - 20 Feb 2019
Cited by 83 | Viewed by 9832
Abstract
Multiplexed platforms for multiple epitope detection have emerged in the last years as very powerful tools to study tumor tissues. These revolutionary technologies provide important visual techniques for tumor examination in formalin-fixed paraffin-embedded specimens to improve the understanding of the tumor microenvironment, promote [...] Read more.
Multiplexed platforms for multiple epitope detection have emerged in the last years as very powerful tools to study tumor tissues. These revolutionary technologies provide important visual techniques for tumor examination in formalin-fixed paraffin-embedded specimens to improve the understanding of the tumor microenvironment, promote new treatment discoveries, aid in cancer prevention, as well as allowing translational studies to be carried out. The aim of this review is to highlight the more recent methodologies that use multiplexed staining to study simultaneous protein identification in formalin-fixed paraffin-embedded tumor tissues for immune profiling, clinical research, and potential translational analysis. New multiplexed methodologies, which permit the identification of several proteins at the same time in one single tissue section, have been developed in recent years with the ability to study different cell populations, cells by cells, and their spatial distribution in different tumor specimens including whole sections, core needle biopsies, and tissue microarrays. Multiplexed technologies associated with image analysis software can be performed with a high-quality throughput assay to study cancer specimens and are important tools for new discoveries. The different multiplexed technologies described in this review have shown their utility in the study of cancer tissues and their advantages for translational research studies and application in cancer prevention and treatments. Full article
(This article belongs to the Special Issue Towards New Promising Discoveries for Lung Cancer Patients: A Selection of Papers from the First Joint Meeting on Lung Cancer of the FHU OncoAge (Nice, France) and the MD Anderson Cancer Center (Houston, TX, USA))
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12 pages, 2730 KiB  
Review
Integrated Approaches for the Use of Large Datasets to Identify Rational Therapies for the Treatment of Lung Cancers
by Robert J. Cardnell, Lauren Averett Byers and Jing Wang
Cancers 2019, 11(2), 239; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers11020239 - 19 Feb 2019
Cited by 1 | Viewed by 3513
Abstract
The benefit and burden of contemporary techniques for the molecular characterization of samples is the vast amount of data generated. In the era of “big data”, it has become imperative that we develop multi-disciplinary teams combining scientists, clinicians, and data analysts. In this [...] Read more.
The benefit and burden of contemporary techniques for the molecular characterization of samples is the vast amount of data generated. In the era of “big data”, it has become imperative that we develop multi-disciplinary teams combining scientists, clinicians, and data analysts. In this review, we discuss a number of approaches developed by our University of Texas MD Anderson Lung Cancer Multidisciplinary Program to process and utilize such large datasets with the goal of identifying rational therapeutic options for biomarker-driven patient subsets. Large integrated datasets such as the The Cancer Genome Atlas (TCGA) for patient samples and the Cancer Cell Line Encyclopedia (CCLE) for tumor derived cell lines include genomic, transcriptomic, methylation, miRNA, and proteomic profiling alongside clinical data. To best use these datasets to address urgent questions such as whether we can define molecular subtypes of disease with specific therapeutic vulnerabilities, to quantify states such as epithelial-to-mesenchymal transition that are associated with resistance to treatment, or to identify potential therapeutic agents in models of cancer that are resistant to standard treatments required the development of tools for systematic, unbiased high-throughput analysis. Together, such tools, used in a multi-disciplinary environment, can be leveraged to identify novel treatments for molecularly defined subsets of cancer patients, which can be easily and rapidly translated from benchtop to bedside. Full article
(This article belongs to the Special Issue Towards New Promising Discoveries for Lung Cancer Patients: A Selection of Papers from the First Joint Meeting on Lung Cancer of the FHU OncoAge (Nice, France) and the MD Anderson Cancer Center (Houston, TX, USA))
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12 pages, 630 KiB  
Review
New Insights into Long Non-Coding RNA MALAT1 in Cancer and Metastasis
by Yutong Sun and Li Ma
Cancers 2019, 11(2), 216; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers11020216 - 13 Feb 2019
Cited by 200 | Viewed by 10864
Abstract
Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is one of the most abundant, long non-coding RNAs (lncRNAs) in normal tissues. This lncRNA is highly conserved among mammalian species, and based on in vitro results, has been reported to regulate alternative pre-mRNA splicing [...] Read more.
Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is one of the most abundant, long non-coding RNAs (lncRNAs) in normal tissues. This lncRNA is highly conserved among mammalian species, and based on in vitro results, has been reported to regulate alternative pre-mRNA splicing and gene expression. However, Malat1 knockout mice develop and grow normally, and do not show alterations in alternative splicing. While MALAT1 was originally described as a prognostic marker of lung cancer metastasis, emerging evidence has linked this lncRNA to other cancers, such as breast cancer, prostate cancer, pancreatic cancer, glioma, and leukemia. The role described for MALAT1 is dependent on the cancer types and the experimental model systems. Notably, different or opposite phenotypes resulting from different strategies for inactivating MALAT1 have been observed, which led to distinct models for MALAT1′s functions and mechanisms of action in cancer and metastasis. In this review, we reflect on different experimental strategies used to study MALAT1′s functions, and discuss the current mechanistic models of this highly abundant and conserved lncRNA. Full article
(This article belongs to the Special Issue Towards New Promising Discoveries for Lung Cancer Patients: A Selection of Papers from the First Joint Meeting on Lung Cancer of the FHU OncoAge (Nice, France) and the MD Anderson Cancer Center (Houston, TX, USA))
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12 pages, 2547 KiB  
Review
Lung Cancer Screening, towards a Multidimensional Approach: Why and How?
by Jonathan Benzaquen, Jacques Boutros, Charles Marquette, Hervé Delingette and Paul Hofman
Cancers 2019, 11(2), 212; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers11020212 - 12 Feb 2019
Cited by 26 | Viewed by 4920
Abstract
Early-stage treatment improves prognosis of lung cancer and two large randomized controlled trials have shown that early detection with low-dose computed tomography (LDCT) reduces mortality. Despite this, lung cancer screening (LCS) remains challenging. In the context of a global shortage of radiologists, the [...] Read more.
Early-stage treatment improves prognosis of lung cancer and two large randomized controlled trials have shown that early detection with low-dose computed tomography (LDCT) reduces mortality. Despite this, lung cancer screening (LCS) remains challenging. In the context of a global shortage of radiologists, the high rate of false-positive LDCT results in overloading of existing lung cancer clinics and multidisciplinary teams. Thus, to provide patients with earlier access to life-saving surgical interventions, there is an urgent need to improve LDCT-based LCS and especially to reduce the false-positive rate that plagues the current detection technology. In this context, LCS can be improved in three ways: (1) by refining selection criteria (risk factor assessment), (2) by using Computer Aided Diagnosis (CAD) to make it easier to interpret chest CTs, and (3) by using biological blood signatures for early cancer detection, to both spot the optimal target population and help classify lung nodules. These three main ways of improving LCS are discussed in this review. Full article
(This article belongs to the Special Issue Towards New Promising Discoveries for Lung Cancer Patients: A Selection of Papers from the First Joint Meeting on Lung Cancer of the FHU OncoAge (Nice, France) and the MD Anderson Cancer Center (Houston, TX, USA))
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13 pages, 258 KiB  
Review
Non-Smoking-Associated Lung Cancer: A distinct Entity in Terms of Tumor Biology, Patient Characteristics and Impact of Hereditary Cancer Predisposition
by Elisabeth Smolle and Martin Pichler
Cancers 2019, 11(2), 204; https://doi.org/10.3390/cancers11020204 - 10 Feb 2019
Cited by 47 | Viewed by 6178
Abstract
Non-small cell lung cancer (NSCLC) in non-, and especially in never-smoking patients is considered a biologically unique type of lung cancer, since risk factors and tumorigenic conditions, other than tobacco smoke, come into play. In this review article, we comprehensively searched and summarized [...] Read more.
Non-small cell lung cancer (NSCLC) in non-, and especially in never-smoking patients is considered a biologically unique type of lung cancer, since risk factors and tumorigenic conditions, other than tobacco smoke, come into play. In this review article, we comprehensively searched and summarized the current literature with the aim to outline what exactly triggers lung cancer in non-smokers. Changes in the tumor microenvironment, distinct driver genes and genetic pathway alterations that are specific for non-smoking patients, as well as lifestyle-related risk factors apart from tobacco smoke are critically discussed. The data we have reviewed highlights once again the importance of personalized cancer therapy, i.e., careful molecular and genetic assessment of the tumor to provide tailored treatment options with optimum chances of good response—especially for the subgroups of never-smokers. Full article
(This article belongs to the Special Issue Towards New Promising Discoveries for Lung Cancer Patients: A Selection of Papers from the First Joint Meeting on Lung Cancer of the FHU OncoAge (Nice, France) and the MD Anderson Cancer Center (Houston, TX, USA))

Other

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11 pages, 1470 KiB  
Perspective
The OncoAge Consortium: Linking Aging and Oncology from Bench to Bedside and Back Again
by Paul Hofman, Nicholas Ayache, Pascal Barbry, Michel Barlaud, Audrey Bel, Philippe Blancou, Frédéric Checler, Sylvie Chevillard, Gael Cristofari, Mathilde Demory, Vincent Esnault, Claire Falandry, Eric Gilson, Olivier Guérin, Nicolas Glaichenhaus, Joel Guigay, Marius Ilié, Bernard Mari, Charles-Hugo Marquette, Véronique Paquis-Flucklinger, Frédéric Prate, Pierre Saintigny, Barbara Seitz-Polsky, Taycir Skhiri, Ellen Van Obberghen-Schilling, Emmanuel Van Obberghen and Laurent Yvan-Charvetadd Show full author list remove Hide full author list
Cancers 2019, 11(2), 250; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers11020250 - 21 Feb 2019
Cited by 2 | Viewed by 4109
Abstract
It is generally accepted that carcinogenesis and aging are two biological processes, which are known to be associated. Notably, the frequency of certain cancers (including lung cancer), increases significantly with the age of patients and there is now a wealth of data showing [...] Read more.
It is generally accepted that carcinogenesis and aging are two biological processes, which are known to be associated. Notably, the frequency of certain cancers (including lung cancer), increases significantly with the age of patients and there is now a wealth of data showing that multiple mechanisms leading to malignant transformation and to aging are interconnected, defining the so-called common biology of aging and cancer. OncoAge, a consortium launched in 2015, brings together the multidisciplinary expertise of leading public hospital services and academic laboratories to foster the transfer of scientific knowledge rapidly acquired in the fields of cancer biology and aging into innovative medical practice and silver economy development. This is achieved through the development of shared technical platforms (for research on genome stability, (epi)genetics, biobanking, immunology, metabolism, and artificial intelligence), clinical research projects, clinical trials, and education. OncoAge focuses mainly on two pilot pathologies, which benefit from the expertise of several members, namely lung and head and neck cancers. This review outlines the broad strategic directions and key advances of OncoAge and summarizes some of the issues faced by this consortium, as well as the short- and long-term perspectives. Full article
(This article belongs to the Special Issue Towards New Promising Discoveries for Lung Cancer Patients: A Selection of Papers from the First Joint Meeting on Lung Cancer of the FHU OncoAge (Nice, France) and the MD Anderson Cancer Center (Houston, TX, USA))
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