Second Line Treatment Of Non Small Cell Lung Cancer Clinical Pathological And Molecular Aspects Of Novel Promising Drugs

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.

This volume focuses on the clinical applications of molecular diagnosis and targeted therapy from the viewpoint of oncologists specializing in specific organs. In addition, it discusses the role of molecular diagnosis and targeted therapy in the course of surgical treatment. Recent, rapid advances in molecular biology have shed new light on the mechanisms of cancer progression, and molecularly targeted drugs have been used to treat a variety of malignant diseases. For the diagnosis and precise treatment of cancer, analysis of the molecular background of the tumor is indispensable. However, there are both tumor-specific and comprehensive mechanisms involved in these processes. Accordingly, a firm grasp of molecular diagnosis and targeted therapies for different tumors is vital for clinicians and basic researchers alike. This book provides essential information and the latest findings on molecular diagnosis and targeted therapy for thoracic and gastrointestinal malignancies. Though primarily intended for clinical and basic oncologists, it also offers a useful guide for clinicians who are interested in this field and are considering getting started in molecular diagnosis and targeted therapy.

Lung cancer is the most common form of cancer in the world and a major cause of death. This new book brings together stellar research from around the world. The two main types of primary lung cancer, small cell and non-small cell are examined. The book's scope encompasses the three main types of non-small cell lung cancer: squamous cell carcinoma which is the commonest type of lung cancer and develops in the cells which line the airways; adenocarcinoma develops from the cells which produce mucus in the lining of the airways; and large cell carcinoma gets its name from the large, rounded cells that are seen when they are examined under the microscope. About 1 in 5 lung cancers are small cell, the rest non-small cell. Causes of lung cancer are primarily smoking, but include as well exposure to radon, asbestos, uranium, arsenic, and certain petroleum products. Research and new drugs are appearing with increasing frequency in this field.

This book analyzes all aspects of metronomic chemotherapy, a new approach involving low-dose, long-term, and frequently administered therapy that has preclinical and clinical activity in various tumors. After an opening section on the pharmacological bases of metronomic chemotherapy, including its antiangiogenic effects and impact on immunity, preclinical studies on various classes of drug are discussed. Clinical applications of metronomic chemotherapy in a wide variety of tumors are then addressed in detail, with description of the results of all published studies. The clinical pharmacology of metronomic chemotherapy is also considered in depth, encompassing pharmacokinetics, pharmacogenetics, pharmacoeconomics, and adverse drug reactions. The book closes by describing the role of this therapy in the veterinarian clinic.

As with other books in the Molecular Pathology Library Series, Molecular Pathology of Lung Cancer bridges the gap between the molecular specialist and the clinical practitioner, including the surgical pathologist who now has a key role in decisions regarding molecular targeted therapy for lung cancer. Molecular Pathology of Lung Cancer provides the latest information and current insights into the molecular basis for lung cancer, including precursor and preinvasive lesions, molecular diagnosis, molecular targeted therapy, molecular prognosis, molecular radiology and related fields for lung cancer generally and for the specific cell types. As many fundamental concepts about lung cancer have undergone revision in only the past few years, this book will likely be the first to comprehensively cover the new molecular pathology of lung cancer. It provides a foundation in this field for pathologists, medical oncologists, radiation oncologists, thoracic surgeons, thoracic radiologists and their trainees, physician assistants, and nursing staff.

This book reviews the current applications of molecular tools in cytopathology and provides a concise handbook for those who provide care in this era of personalized medicine. Specifically, the text provides a comprehensive and concise review of the emerging molecular tests available clinically in different subspecialities of diagnostic pathology. It reviews the current data of molecular testing already applied in cytopathology, discusses some of the biomarkers with potential utility in cytopathology in the near future and reviews the technical challenges in applying and validating molecular tools in liquid-based cytologic materials. Molecular Cytopathology will serve as a valuable resource for cytopathologists, cytotechnologists, pathology trainees, and clinicians with an interest in molecular applications in cytopathology.

Cancer is a very aggressive disease and currently it has been considered a challenge to oncologists and cancer patients worldwide. Nowadays, several therapeutic strategies had improved toward last decades. Surgery is many times still the best curative treatment, mainly in early stage disease. However, Radiotherapy and chemotherapy acquired a main role in this scenario. Target therapies were introduced for medical oncology practice and are demonstrating a hallmark of a new era in cancer treatment. More recently, immunotherapy has been considered the novel cornerstone in cancer treatment. The 2nd edition of the International Manual of Oncology Practice (iMOP) emerged after the great success of the iMOP 1st edition as a reference for medical oncologists and medical residents in the field. In this edition, several chapters were revised and its addresses from the molecular issues of cancer sciences to the clinical practice in medical oncology. In addition, multiple choice questions and clinical cases were included in the main chapters in order to improve the reader learning. The book focuses systemic treatments in many areas of medical oncology, such as breast cancer, gastrointestinal, thoracic, urological oncology, head and neck tumors, bone tumors, sarcomas and palliative care. The topics herein discussed will provide the readers a step forward in the medical oncology practice understanding and give facilities for help in cancer patient treatments.