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Lung cancer is the number one cause of cancer deaths around the world. This devastating disease takes strength not only in people who smoke but also in poor people that eat polluted food and use heating sources, and in those exposed naturally to toxic compounds present in indoor and outdoor environments. Lung cancer patients and their families wait actions from the science that give not only answer to their demands but also a light of hope at the moment of receiveing the diagnosis. This book meets the experience of several researchers who dedicate many hours a day to find not only the cure of lung cancer but also the way to convert the pathology of this chronic disease. In 12 chapters, the lectures will give information related to the relationship of lung cancer and smoking habit, the crucial role of the image technology for diagnosis of lung cancer, and a molecular vision of prevention, diagnosis, and treatment of lung cancer. The authors with a clinic and/or lab vision and with a great spirit to collaborate with the science and with each past, present, and future patient and their families have dedicated many hours to write each chapter. Probably, the final answer to find the cure of lung cancer is not in this book. However, the lectures will give scientific information that will contribute in the near future improvement to the life quality of the patients.

Lungs --- Cancer. --- Lung cancer --- Medicine --- Pulmonology --- Internal Medicine --- Health Sciences

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"West’s Pulmonary Pathophysiology: The Essentials offers accessible explanations of disease processes that affect the respiratory system. This best-selling companion to West’s Respiratory Physiology, Tenth Edition, has served generations of students. Dr. John B. West, together with new co-author Dr. Andrew M. Luks, presents the vital knowledge you need in a concise, straightforward manner that’s easy to understand." -- Publisher.

Lung Diseases --- Respiratory Function Tests --- Lung --- Function Test, Pulmonary --- Function Tests, Pulmonary --- Pulmonary Function Test --- Test, Pulmonary Function --- Tests, Pulmonary Function --- Lung Function Tests --- Pulmonary Function Tests --- Function Test, Lung --- Function Test, Respiratory --- Function Tests, Lung --- Function Tests, Respiratory --- Lung Function Test --- Respiratory Function Test --- Test, Lung Function --- Test, Respiratory Function --- Tests, Lung Function --- Tests, Respiratory Function --- physiopathology --- pathology --- physiopathology. --- pathology. --- Respiratory Function Tests. --- Lungs --- Pulmonary function tests. --- Pathophysiology. --- Pathological physiology. Pathogenesis --- Pathology of the respiratory system

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Pulmonary Disease, Chronic Obstructive --- Lungs --- Poumons --- Diseases, Obstructive --- Maladies obstructives --- Lung Diseases, Obstructive --- Poumon --- Bronchopneumopathies obstructives --- Maladies --- Lung Diseases, Obstructive. --- Pulmonary Disease, Chronic Obstructive. --- Bronchopneumopathies obstructives. --- Maladies.

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Les mutations somatiques, responsables de l’apparition et du développement des cancers, ont de multiples origines (exposition à carcinogène ou infidélité de l’ADN polymérase). On appelle signature mutationnelle l’ensemble des altérations laissées dans le génome par un processus mutationnel. Après celle attribuée à l’âge, la signature mutationnelle la plus fréquemment retrouvée dans les tumeurs est associée à l’activité désaminase des protéines APOBEC3 (Apolipoprotein B Editing Catalytic subunits 3, A3). Ces enzymes, au nombre de 7 (A3A, B, C, DE, F, G and H) chez l’homme et impliquées dans l’immunité innée antivirale, convertissent la déoxycytidine de l’ADN en uridine. Dans les tumeurs du cou et de la gorge positives aux papillomavirus humains, des mutations attribuées aux A3s sont observées, alors qu’elles sont absentes des tumeurs oro-pharyngées négatives pour ce virus. Cette étude a donc établi un premier lien entre une infection virale et la signature mutationelle caractéristique des A3s. Bien que ces signatures soient également très répandues dans les cancers du poumon non à petites cellules, aucun lien n’a encore été établi avec une possible infection virale.
Le but de ce travail a donc été d’étudier si certaines souches d’adénovirus (HAdV) fréquemment impliquées dans les infections du système respiratoire inférieur, à savoir l’HAdV-C2, l’HAdV-C5 et l’HAdV-B3, peuvent induire l’expression des enzymes APOBEC3, et plus particulièrement du membre APOBEC3B, au sein de cellules épithéliales pulmonaires. Nous avons mis en évidence que seule l’expression des transcrits A3B est induite par les 3 souches adénovirales dans des cellules épithéliales pulmonaires cancéreuses A549. Nous avons également détecté l’expression de protéines A3B suite à l’infection par les souches C2 et B3. De manière intéressante, les deux souches virales induisent l’expression de protéines A3B ayant des poids moléculaires légèrement différents. Nous émettons l’hypothèse que cette différence est due à des modifications post-traductionnelles. Bien qu’ils doivent être confirmés par des expériences supplémentaires, ces résultats sont très encourageants et pourraient être le point de départ du premier lien entre infection virale et les mutations associées aux APOBEC3s dans le cancer du poumon non à petites cellules. Somatic mutations, which are responsible for the emergence and development of cancers, have multiple origins, such as the exposition to carcinogenic agents or the DNA polymerase infidelity during replication. After the spontaneous mutations associated with age, the second most prevalent mutational process has been attributed to the deaminase activity of APOBEC3 proteins (Apolipoprotein B Editing Catalytic subunits 3, A3). This family of enzymes, which contains 7 members (A3A, B, C, DE, F, G and H) in humans and involved in innate immune defenses against viruses, converts cytosine bases to uracil in single stranded DNA contexts. Genomic mutations associated with APOBEC3 are observed in human papillomavirus (HPV) positive head and neck squamous cell carcinomas, whereas they are lacking in HPV negative oropharyngeal cancer. This study established the first link between viral infection and APOBEC3-associated mutations. Although these mutations are also common in non-small cell lung cancer, no link has yet been established with a possible viral infection.
The aim of this project was to test whether adenoviral strains (HAdV) frequently involved in lower respiratory tract infections (HAdV-C2, HAdV-C5 and HAdV-B3) induce the expression of APOBEC3 enzymes in pulmonary epithelial cells. We founded that A3B transcripts are the only ones that are upregulated upon adenoviral infection in A549 cancerous pulmonary epithelial cells. We also detected the expression of A3B at the protein level upon infection by the B3 and C2 strains. Very interestingly, the induced A3B proteins showed a slight different molecular weight. We hypothesize that this difference might be caused by different post-translational modifications. Although they must be confirmed by other experiments, these results are very encouraging and may be the starting point for the first link between viral infection and APOBEC3-associated mutation in non-small cell lung cancer.

APOBEC3 --- cytidine deaminase --- lung cancer --- virus --- respiratory infection --- Sciences du vivant > Biochimie, biophysique & biologie moléculaire

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Lung cancer still remains a challenging disease with a higher mortality rate in comparison to other cancers. The discovery of oncogene addicted tumours and targeted therapies responsive to these targets lead to a meaningful change in the prognosis of these diseases. Unfortunately, these newer therapeutic options are reserved to a minor part of lung cancer patients harbouring specific mutations. In the so called wild type population, the first line options bring the median overall survival to go beyond 1 year, and in the population receiving the maintenance therapy over 16 months. Given these results, more than 60% of patients may receive a second line therapy with further opportunities to improve the length and quality of life. For patients not harbouring targetable DNA mutations newer options will be available for second line therapeutic schemes and two major assets seem to be promising: immune modulation and anti-angiogenetic agents. In particular, anti PD1/PDL1 antibodies, VEGFR antibodies and TKIs, these latter combined with standard chemotherapy docetaxel advance the median overall survival of 12 months. These drugs have a different mechanism of action, various adverse events and their activity is different depending on the types of population. However, the biomarkers’ activity and efficacy prediction are not fully or totally understood. In addition, also for patients with DNA targetable mutations new drugs seems to be promising for the use in the second line therapeutic protocols. In particular, drugs selectively directed against ALK translocation and mutational events and EGFR T790M secondary mutations seems to be very promising. In this Research Topic we critically discuss the older therapies and the historical development of second line, putting in to perspective the new agents available in clinical practice. We discuss their importance from a clinical point of view, but also consider and exploit the complex molecular mechanisms responsible of their efficacy or of the subsequently observed resistance phenomena. In this perspective, the undercovering and characterization of novel predictive biomarkers by NGS technology, the characterization of novel actors in the signal transduction pathway modulating the response of the cells, the optimization of new diagnostic tool as the evaluation of liquid biopsy and the implementation of more suitable pre-clinical models are crucial aspects dissected too. Nivolumab, nintedanib and ramucirumab probably will give the opportunity to improve the efficacy outcomes for the treatment of wild type tumours in second line therapeutic schemes, but many aspects should be debated in order that these agents are made available to patients, planning ahead a therapeutic strategy, beginning from the first line therapy, to the subsequent ones in a logical and affordable manner. As well, for treatment of mutated tumours, mutated EGFR irreversible inhibitors such as rociletinib and AZD9291, and ALK targeting drugs ceritinib and alectinib will also play an important role in the immediate future. Probably the right way is to give all the available opportunities to patients, but challenges and pitfalls should be carefully debated, and by launching this Research Topic we tried to give some practical insights in this changing landscape.

Alectinib --- Liquid Biopsy --- Non-Small Cell Lung Cancer --- Afatinib --- Nivolumab --- Immunotherapy --- Nintedanib --- Dacomitinib --- Second-Line Treatment --- Tyrosine Kinase Inhibitor