Radiation therapy has played a key role, together with surgery and systemic chemotherapy, in treating in all stages of non-small cell lung cancer. We have witnessed remarkable improvements in radiation therapy techniques, with the innovations in hardware and software. Stereotactic ablative radiation therapy, which can deliver high radiation dose focused to small target volume, represents one of the state-of-the-art radiation therapy techniques. The technical development of radiation therapy and the role of stereotactic ablative radiation therapy in treating inoperable stage I non-small cell lung cancer are briefly reviewed.
Carcinoma, Non-Small-Cell Lung* ; Drug Therapy ; Radiotherapy ; Stereotaxic Techniques

Lung cancer is the most common cause of cancer death worldwide. With advances in understanding of lung cancer biology and technology, there has been significant improvement in the treatment of non-small-cell lung cancer (NSCLC) during the last decades through the development of targeted agents for molecular subgroups harboring specific genomic abnormalities. So far, agents targeting Epidermal growth factor receptor (EGFR) and Anaplastic Lymphoma Kinase (ALK) have led to high and durable response rates in patients with EGFR mutation or ALK translocation. Also agents targeting VEGF improved overall survival even though a specific biomarker has not been defined yet. As more and more genomic alterations, such as ROS1, RET, MET, HER2, BRAF, FGFR1, DDR2, PI3KCA and K-ras, are being identified in NSCLC, new targeted agents for patients with specific genomic alterations have been developed and have showed promising results. Furthermore, promising results with immune checkpoint inhibitors such as CTLA4 inhibitors, PD-1 or PDL-1 antibody will shed light on further improvement of treatment of lung cancer in the near future. However, the evolving nature of cancer through the appearance of resistance to targeted agents and tumor heterogeneity would provide much challenge to conquer lung cancer. Unfortunately, since no significant progress has been achieved in targeted agents in small cell lung cancer, this review will focus on NSCLC and provides an overview of growing new targeted agents in the treatment of NSCLC.
Biology ; Carcinoma, Non-Small-Cell Lung ; Humans ; Lung Neoplasms* ; Lung* ; Lymphoma ; Molecular Targeted Therapy* ; Phosphotransferases ; Population Characteristics ; Receptor, Epidermal Growth Factor ; Small Cell Lung Carcinoma ; Vascular Endothelial Growth Factor A

Non-small-cell lung cancer is one of the leading causes of deaths from cancer worldwide. There have been remarkable advances in the targeted treatment of advanced non-small cell lung cancer (NSCLC) over the past several years. Survival outcomes are steadily improving as management paradigms shift in the diagnosis and treatment of advanced NSCLC. Customizing treatment based on histology and molecular typing has become a standard of care in this era of targeted therapy. Even as new chemotherapeutic agents are proving effective, a pivotal role for platinum-based chemotherapy doublets has been confirmed. Maintenance chemotherapy has become an option, but determining which patients will most benefit from it remains controversial in the real-world setting. Ongoing efforts to overcome resistance to targeted agents utilizing combination regimens of chemotherapy plus targeted agents, are currently being explored and optimized. This review highlights recent developments in novel chemotherapeutics. Despite advances in molecular medicine, there remains an essential role for chemotherapy in advanced NSCLC, even in the recent targeted therapy era.
Antineoplastic Agents ; Carcinoma, Non-Small-Cell Lung* ; Cause of Death ; Chemotherapy, Adjuvant ; Diagnosis ; Drug Therapy* ; Humans ; Lung Neoplasms ; Maintenance Chemotherapy ; Molecular Medicine ; Molecular Typing ; Standard of Care

The progression to minimally invasive techniques has been almost a natural evolution of the use of video-assisted thoracic surgery (VATS) from the investigation of pleural diseases, such as pneumothorax, and pleural effusion. Surgical resection is the primary treatment for early-stage non-small cell lung cancer (NSCLC). Minimally invasive thoracic surgery has been extensively used in the field of lung cancer. As the procedure has evolved and been studied, thoracoscopic lobectomy has been demonstrated to be a safe and oncologically effective strategy in the surgical management of patients with early stage NSCLC. VATS is a minimally invasive technique that has many advantages in postoperative pain and recovery time. Most surgeons perform VATS for lung cancer with three or more incisions. As the technique of VATS has evolved, single- or double-port VATS for lung cancer has been recently attempted and its advantages have been reported.
Carcinoma, Non-Small-Cell Lung ; Humans ; Lung Neoplasms* ; Lung* ; Pain, Postoperative ; Pleural Diseases ; Pleural Effusion ; Pneumothorax ; Thoracic Surgery* ; Thoracic Surgery, Video-Assisted

Convex-probe endobronchial ultrasound-guided transbronchial needle aspiration (CP-EBUS-TBNA) has emerged as a new diagnostic modality that allows ultrasound-guided, real-time needle aspiration of mediastinal and hilar lymph nodes. Mediastinoscopy has been the reference standard for neoplastic staging in the mediastinum, but it is invasive and requires general anesthesia. Considering recent prospective studies and clinical guidelines, a needle technique such as EBUS-TBNA and endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) should be performed first for the mediastinal nodal staging of non-small lung cancer. Combining EBUS-TBNA and EUS-FNA will replace more invasive methods such as mediastinoscopy. CP-EBUS-TBNA can also be used for the restaging after neoadjuvant therapy, the diagnosis of recurrent lung cancer and central lung parenchymal lesion which abuts trachea or bronchi. In the era of personalized medicine, good-quality and sufficient tissues need to be obtained for the molecular testing and treatment guidance. EBUS-TBNA has the ability to obtain satisfactory material for the detection of EGFR mutation, KRAS mutation, and EML-ALK fusion gene.
Anesthesia, General ; Bronchi ; Diagnosis* ; Endoscopic Ultrasound-Guided Fine Needle Aspiration ; Lung Neoplasms* ; Lung* ; Lymph Nodes ; Mediastinoscopy ; Mediastinum ; Methods ; Needles ; Neoadjuvant Therapy ; Neoplasm Metastasis ; Trachea ; Precision Medicine

Lung cancer is the leading cause of cancer-related mortality worldwide, including in Korea. Although various treatment modalities have been developed, the prognosis of patients with lung cancer is still very unfavorable. Most patients with lung cancer are diagnosed at an advanced stage, and palliative care remains the only therapeutic option for these patients. Accordingly, early detection of lung cancer may lead to a decrease in lung cancer-related mortality. Therefore, considerable interest has been generated in the development of screening tools to detect lung cancer at an early stage. Although chest radiography and sputum cytological evaluation have been used to screen patients for lung cancer, the sensitivity and specificity of these procedures are not adequate. Recently, low-dose computed tomography (LDCT) has emerged as a promising screening technique, and several trials have demonstrated its benefit in the high-risk population. One such well-designed and well-conducted trial, the National Lung Screening Trial (NLST), showed a 20% reduction in lung cancer-related mortality. Based on the results of NLST and other trials, screening for lung cancer using LDCT is recommended in asymptomatic patients who are at a high risk for lung cancer, with regard to age and smoking history. The present report is a comprehensive review of available evidence on the benefits and risks of lung cancer screening and summarizes some recommendations.
Early Detection of Cancer ; Humans ; Korea ; Lung Neoplasms* ; Lung* ; Mass Screening* ; Mortality ; Palliative Care ; Prognosis ; Radiography ; Risk Assessment ; Sensitivity and Specificity ; Smoke ; Smoking ; Sputum ; Thorax ; Tomography, X-Ray Computed

Lung cancer is characterized by accumulation of oncogene activation, inactivation of tumor suppressor genes and alteration of epigenetic changes. Fortunately, the past decade has seen remarkable development in molecular pathogenesis and management of lung cancer, especially adenocarcinoma. The discovery of the biologic and therapeutic importance of acquired genetic alterations in 2 genes that encode pharmacologically targetable tyrosine kinases involved in growth factor receptor signaling, epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK), has raised hope that targeted therapy will improve survival and quality of life of patients with lung cancer. Therefore, molecular testing to detect these 2 mutated genes is more important than ever and has changed the management of the patients with lung cancer and the role of pathologists. Furthermore, as most lung cancer patients present with advanced-stage disease at the time of diagnosis, it is important to detect targetable mutations using small tissue samples or cytology specimens. Here, the author summarizes the practical impact of the molecular testing of lung cancer and introduces the current knowledge of lung cancer pathology.
Adenocarcinoma ; Diagnosis ; Epigenomics ; Genes, Tumor Suppressor ; Hope ; Humans ; Lung Neoplasms* ; Lung* ; Lymphoma ; Molecular Diagnostic Techniques ; Oncogenes ; Pathology* ; Phosphotransferases ; Quality of Life ; Receptor, Epidermal Growth Factor ; Tyrosine

In the past decades, substantial developments in the understanding of molecular biology in non-small-cell lung cancer (NSCLC) have improved diagnosis and treatment of NSCLC based on the genotype of each patient's tumor. For example, gain-of function mutations of epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) rearrangement are sensitive biomarkers in predicting tumor response and survival to EGFR tyrosine kinase inhibitor and ALK inhibitor, respectively. However, since NSCLC is one of the most complex and heterogenous cancers and the leading cause of cancer-related death in the world, there are still many challenges for prevention, diagnosis, and treatment of NSCLC. This review summarizes the molecular biology of NSCLC including activation of oncogenes, suppression of tumor suppressor genes, angiogenesis, epigenetic alteration, microRNA, telomerase, cancer stem cell, and cancer genomics using next generation sequencing methods.
Carcinoma, Non-Small-Cell Lung ; Diagnosis ; Epigenomics ; Genes, Tumor Suppressor ; Genomics ; Genotype ; High-Throughput Nucleotide Sequencing ; Lung Neoplasms* ; Lung* ; Lymphoma ; Methods ; MicroRNAs ; Molecular Biology* ; Neoplastic Stem Cells ; Oncogenes ; Phosphotransferases ; Protein-Tyrosine Kinases ; Receptor, Epidermal Growth Factor ; Telomerase ; Biomarkers

Over the last decades, piles of data have been accumulated to understand the olfactory sensation in every aspect, ranging from the intracellular signaling to cognitive perception. This review focuses on the ion conduction through multiple ion channels expressed in olfactory sensory neurons (OSNs) to describe how odorant binding to olfactory receptors is transduced into an electrical signal. Olfactory signal transduction and the generation of the depolarizing receptor current occur in the cilia, where the unique extraciliary environment of the nasal mucosa assists in the neuronal activation. Upon contacting with odorants, OSNs dissociate G protein-coupled receptors, initiating a signal transduction pathway that leads to firing of action potential. This signaling pathway has a unique, two step organization: a cAMP-gated Ca2+ (CNG) channel and a Ca2+-activated Cl- channel (CACC), both of which contribute to signal amplification. This transduction mechanism requires an outward-directed driving force of Cl- established by active accumulation of Cl- within the lumen of the sensory cilia. To permit Cl- accumulation, OSNs avoid the expression of the 'Chloride Sensor: WNK3', that functions as the main Cl- exclusion co-transporter in neurons of the central nervous system (CNS). Cl- accumulation provides OSNs with the driving force for the depolarization, increasing the excitatory response magnitude. This is an interesting adaptation because of the fact that the olfactory cilia reside in the mucus, outside the body, where the concentrations of ions are not as well regulated as they are in normal interstitial compartments.
Action Potentials ; Central Nervous System ; Cilia ; Fires ; Ion Channels ; Ions ; Mucus ; Nasal Mucosa ; Neurons ; Odors ; Olfactory Receptor Neurons ; Sensation ; Sensory Receptor Cells* ; Signal Transduction ; Smell

Animals find nutritious foods to survive, while avoiding aversive and toxic chemicals through the chemosensory faculties of olfaction and taste. The olfaction is comparatively well characterized, but the studies of taste are only recently developing since after 2000. Genetic, immunohistochemistry, and electrophysiological studies with knock-out transgenic mice opened up the taste field in mammals. Taste in insects has been only recently been studied after mammalian taste receptors were identified. Flies also discriminate the differences of sweet, salty and sour food, while being able to detect and reject potential foods contaminated with toxins or detrimental chemicals. These discriminatory abilities indicate that flies house basic taste receptors in their taste organs like humans. For the last decade, the sweet and bitter gustatory receptors in Drosophila have been characterized. In this review, we compare the taste anatomy between humans and insects. We also introduce five canonical taste sensations in Drosophila. In addition, we introduce new taste repertoires, that fruit flies can sense water and fatty acids as well as the carbonation buffer in beverage. These studies on simple model organisms will open up a new potential for scientists to further investigate these characteristics in vertebrates.
Animals ; Beverages ; Carbon ; Diptera ; Drosophila* ; Electrophysiology ; Fatty Acids ; Fruit ; Humans ; Immunohistochemistry ; Insects ; Mammals ; Mice ; Mice, Transgenic ; Sensation* ; Smell ; Vertebrates