Genomic mechanisms of transformation from chronic obstructive pulmonary disease to lung cancer. Wang Diane C,Shi Lin,Zhu Zhenhua,Gao Danyan,Zhang Yong Seminars in cancer biology Genetic variations in COPD and lung cancer may be one of the molecular mechanisms responsible for COPD-lung cancer transformation. The present review highlights main genetic variations co-existed in COPD and lung cancer and integrates the varied genes into four molecular mechanisms, e.g. activated cell proliferation pathway, tumor suppressor and DNA repair gene dysfunction, chronic inflammatory microenvironment, and impaired immune response, by which COPD epithelial cells may be transformed into tumorigenic status. We call special attention to further investigate the transformation from COPD to lung cancer and understand the exact molecular mechanisms, to prevent and reduce the increased incidence of COPD and lung cancer. We call direct evidence to show the existence of COPD-lung cancer transformation, since current evidence to support the transformation from COPD to lung cancer is the co-existence of selected genes and proteins in both. We should furthermore explore and understand the homogeneity and heterogeneity of gene mutation, epigenetics, sequencing, and function between COPD and lung cancer. The defining and understanding of COPD-lung cancer transformation will provide new diagnostic and therapeutic biomarkers as a new milestone to prevent and treat lung cancer. 10.1016/j.semcancer.2016.11.001
    Lung Cancer Screening, Version 3.2018, NCCN Clinical Practice Guidelines in Oncology. Wood Douglas E,Kazerooni Ella A,Baum Scott L,Eapen George A,Ettinger David S,Hou Lifang,Jackman David M,Klippenstein Donald,Kumar Rohit,Lackner Rudy P,Leard Lorriana E,Lennes Inga T,Leung Ann N C,Makani Samir S,Massion Pierre P,Mazzone Peter,Merritt Robert E,Meyers Bryan F,Midthun David E,Pipavath Sudhakar,Pratt Christie,Reddy Chakravarthy,Reid Mary E,Rotter Arnold J,Sachs Peter B,Schabath Matthew B,Schiebler Mark L,Tong Betty C,Travis William D,Wei Benjamin,Yang Stephen C,Gregory Kristina M,Hughes Miranda Journal of the National Comprehensive Cancer Network : JNCCN Lung cancer is the leading cause of cancer-related mortality in the United States and worldwide. Early detection of lung cancer is an important opportunity for decreasing mortality. Data support using low-dose computed tomography (LDCT) of the chest to screen select patients who are at high risk for lung cancer. Lung screening is covered under the Affordable Care Act for individuals with high-risk factors. The Centers for Medicare & Medicaid Services (CMS) covers annual screening LDCT for appropriate Medicare beneficiaries at high risk for lung cancer if they also receive counseling and participate in shared decision-making before screening. The complete version of the NCCN Guidelines for Lung Cancer Screening provides recommendations for initial and subsequent LDCT screening and provides more detail about LDCT screening. This manuscript focuses on identifying patients at high risk for lung cancer who are candidates for LDCT of the chest and on evaluating initial screening findings. 10.6004/jnccn.2018.0020
    Non-Small Cell Lung Cancer: Epidemiology, Screening, Diagnosis, and Treatment. Duma Narjust,Santana-Davila Rafael,Molina Julian R Mayo Clinic proceedings Lung cancer remains the leading cause of cancer deaths in the United States. In the past decade, significant advances have been made in the science of non-small cell lung cancer (NSCLC). Screening has been introduced with the goal of early detection. The National Lung Screening Trial found a lung cancer mortality benefit of 20% and a 6.7% decrease in all-cause mortality with the use of low-dose chest computed tomography in high-risk individuals. The treatment of lung cancer has also evolved with the introduction of several lines of tyrosine kinase inhibitors in patients with EGFR, ALK, ROS1, and NTRK mutations. Similarly, immune checkpoint inhibitors (ICIs) have dramatically changed the landscape of NSCLC treatment. Furthermore, the results of new trials continue to help us understand the role of these novel agents and which patients are more likely to benefit; ICIs are now part of the first-line NSCLC treatment armamentarium as monotherapy, combined with chemotherapy, or after definite chemoradiotherapy in patients with stage III unresectable NSCLC. Expression of programmed cell death protein-ligand 1 in malignant cells has been studied as a potential biomarker for response to ICIs. However, important drawbacks exist that limit its discriminatory potential. Identification of accurate predictive biomarkers beyond programmed cell death protein-ligand 1 expression remains essential to select the most appropriate candidates for ICI therapy. Many questions remain unanswered regarding the proper sequence and combinations of these new agents; however, the field is moving rapidly, and the overall direction is optimistic. 10.1016/j.mayocp.2019.01.013
    Acquired resistance to EGFR targeted therapy in non-small cell lung cancer: Mechanisms and therapeutic strategies. Lim Sun Min,Syn Nicholas L,Cho Byoung Chul,Soo Ross A Cancer treatment reviews The tyrosine kinase inhibitors (TKIs) directed at sensitizing mutations in the epidermal growth factor receptor (EGFR) gene represents a critical pillar in non-small cell lung cancer treatment. Despite the excellent disease control with initial EGFR TKI therapy, acquired resistance is ubiquitous and remains a key challenge. Investigations into the mechanisms which foster resistance to EGFR TKIs has led to the discovery of novel biomarkers and drug targets, and in turn has enabled the development of third-generation TKIs and proposals for rational therapeutic combinations. The threonine-to-methionine substitution mutation at position 790 (T790M) is clinically validated to engender refractoriness to first- and second-generation TKIs, and is a standard-of-care predictive biomarker used in therapeutic stratification. Clinical use of liquid biopsy approaches for assessment of T790M mutations continues to increase, with growing advocacy for serial monitoring of tumor evolution. For patients who are T790M-negative, cytotoxic chemotherapy or protracted EGFR TKI treatment are acceptable treatment standards after disease progression, although combinations of targeted therapies and checkpoint blockade immunotherapy may offer promising alternatives in the future. Among T790M-positive patients, the third-generation EGFR TKI, osimertinib, has shown superiority over both platinum-doublet chemotherapy and 1st generation EGFR TKI in randomized clinical trials, and exhibits enhanced in vitro selectivity for mutant EGFR receptors and pharmacokinetics compared to earlier-generation TKIs. This article appraises the key literature on the contemporary management of non-small cell lung cancer patients with acquired resistance to EGFR TKIs, and envisions future directions in translational and clinical research. 10.1016/j.ctrv.2018.02.006
    Overview upon miR-21 in lung cancer: focus on NSCLC. Bica-Pop Cecilia,Cojocneanu-Petric Roxana,Magdo Lorand,Raduly Lajos,Gulei Diana,Berindan-Neagoe Ioana Cellular and molecular life sciences : CMLS Considering the high mortality rate encountered in lung cancer, there is a strong need to explore new biomarkers for early diagnosis and also improved therapeutic targets to overcome this issue. The implementation of microRNAs as important regulators in cancer and other pathologies expanded the possibilities of lung cancer management and not only. MiR-21 represents an intensively studied microRNA in many types of cancer, including non-small cell lung cancer (NSCLC). Its role as an oncogene is underlined in multiple studies reporting the upregulated expression of this sequence in patients diagnosed with this malignancy; moreover, several studies associated this increased expression of miR-21 with a worse outcome within NSCLC patients. The same pattern is supported by the data existent in the Cancer Genome Atlas (TCGA). The carcinogenic advantage generated by miR-21 in NSCLC resides in the target genes involved in multiple pathways such as cell growth and proliferation, angiogenesis, invasion and metastasis, but also chemo- and radioresistance. Therapeutic modulation of miR-21 by use of antisense sequences entrapped in different delivery systems has shown promising results in impairment of NSCLC. Hereby, we review the mechanisms of action of miR-21 in cancer and the associated changes upon tumor cells together a focused perspective on NSCLC signaling, prognosis and therapy. 10.1007/s00018-018-2877-x