Oncogene Directed Therapies

Prominent investigators and clinicians summarize in a balanced blend of fundamental science, basic research, experimental therapeutics, and early clinical experiences, what is known about oncogenes and oncogenesis, and describe how that knowledge can be used to treat the cancer. The contributors explain how, why, and under what conditions certain proteins acquire the ability to transform eukaryotic cells, and detail the crucial biological consequences of this oncogenic transformation, particularly for cellular mitogenesis, survival, differentiation, migration, proteolysis, or angiogenic competence. Their articles thoroughly explicate the premises, principles, techniques, and approaches to oncogene targeting in various types of human cancer by using signal transduction inhibitors, immunological targeting methods, and antisense gene therapy.

In recent years an entirely new category of anticancer agents has entered the clinic. This class of drugs, the frontrunners of which are Herceptin and Gleevec, are no longer a product of the intuitive and largely empirical explorations that brought about traditional anticancer treatments like chemotherapy. Rather, these new agents have emerged directly from molecular analysis of various cancer-causing genes (oncogenes). In Oncogene-Directed Therapies, prominent investigators and clinicians, several of them pioneers in the field, summarize what is known about oncogenes and oncogenesis-in a balanced blend of fundamental science, basic research, experimental therapeutics, and early clinical experience-and describe how that knowledge can be used to treat the disease. The contributors explain how, why, and under what conditions certain proteins acquire the ability to transform eukaryotic cells, and detail the crucial biological consequences of this oncogenic transformation, particularly for cellular mitogenesis, survival, differentiation, migration, proteolysis, or angiogenic competence. Their articles thoroughly explicate the premises, principles, techniques, and approaches to oncogene targeting in various types of human cancer by using signal transduction inhibitors, immunological targeting methods, and antisense gene therapy. Also included is a review of the results of preclinical and clinical testing of some of today's most advanced therapeutic agents. Unique in perspective and comprehensive in its coverage, Oncogene-Directed Therapies not only integrates for all those engaged in-or simply interested in the cutting-edge of-the war on cancer" the many remarkable recent achievements in our molecular understanding and treatment of these diseases, but also clarifies what directions future research might optimally take, as well as what significant accomplishments might lie ahead."

This book contextualizes translational research and provides an up to date progress report on therapies that are currently being targeted in lung cancer. It is now well established that there is tremendous heterogeneity among cancer cells both at the inter- and intra-tumoral level. Further, a growing body of work highlights the importance of targeted therapies and personalized medicine in treating cancer patients. In contrast to conventional therapies that are typically administered to the average patient regardless of the patient’s genotype, targeted therapies are tailored to patients with specific traits. Nonetheless, such genetic changes can be disease-specific and/or target specific; thus, the book addresses these issues manifested in the somatically acquired genetic changes of the targeted gene. Each chapter is written by a leading medical oncologist who specializes in thoracic oncology and is devoted to a particular target in a specific indication. Contributors provide an in-depth review of the literature covering the mechanisms underlying signaling, potential cross talk between the target and downstream signaling, and potential emergence of drug resistance.

This volume explores the mechanisms of resistance to targeted therapeutics. The focus is on the cancer cell signaling network, although other mechanisms of resistance including target mutation, and new areas of study such as cancer stem cells are included. Targeted Therapies: Mechanisms of Resistance highlights examples of changes in the signaling network in response to inhibition of a signaling event and underscores the importance in having a mechanistic understanding of the signaling network in cancer for developing effective targeted cancer therapies. Moreover, cutting edge tools to analyze the cell signaling network will be discussed. This includes the leading edge of techniques as well as computational biology and systems theory. This volume provides the reader with both an overview as well as a detailed perspective on the mechanisms of resistance to targeted therapeutics and will be of great value to the oncologist, the physician-scientist treating patients and the translational scientist working on any aspect of targeted therapeutics.

Targeted therapies were initially developed to exploit the upregulation and dependence on key oncogenic pathways critical to cancer progression. Additionally, they also presented as a method to overcome chemoresistance by supplementing conventional therapeutic regimens with targeted therapies. However, the development of resistance to these combinatorial approaches has led to the reassessment of currently available therapeutic options to overcome resistance to targeted therapy. This book aims to provide an update on the advancements in the therapeutic arms race between cancer, clinicians and scientists alike to overcome resistance to targeted therapies. Subject experts provide a comprehensive overview of the challenges and solutions to resistance to several conventional targeted therapies in addition to providing a discussion on broad topics including targeting components of the tumor microenvironment, emerging therapeutic options, and novel areas to be explored concerning nanotechnology and the epigenome.

This volume provides readers a comprehensive and state-of-the-art overview about the range of applications of targeted therapies for solid tumors. The sections of the book have been structured to review the oncogene addicted tumors, the pharmacology and clinical development of new molecularly targeted agents, the use of biomarkers as prognostic, predictive and surrogate endpoints, and the evaluation of tumor response and specific malignancies treated with targeted agents. The book also covers some of the newest developments in cancer therapy that are not adequately covered by any current available literature. Written by recognized experts in the field, Targeted Therapies for Solid Tumors: A Handbook for Moving Toward New Frontiers in Cancer Treatment provides a unique and valuable resource in the field of molecular oncology, both for those currently in training, and for those already in clinical or research practice.

Differential gene regulation and targeted therapy are the critical aspects of several cancers. This book covers specific gene regulation and targeted therapies in different malignancies. It offers a comprehensive assessment of the transcriptional dysregulation in cancer, and considers some examples of transcriptional regulators as definitive oncogenic drivers in solid tumors, followed by a brief discussion of transcriptional effectors of the programs they drive, and discusses its specific targets. Most targeted therapeutics developed to date have been directed against a limited set of oncogenic drivers, exemplified by those encoding cell surface or cytoplasmic kinases that function in intracellular signaling cascades.