A panel of leading academic and pharmaceutical investigators takes stock of the remarkable work that has been accomplished to date with proteasome inhibitors in cancer, and examines emerging therapeutic possibilities. The topics range from a discussion of the chemistry and cell biology of the proteasome and the rationale for proteasome inhibitors in cancer to a review of current clinical trials underway. The discussion of rationales for testing proteasome inhibitors in cancer models covers the role of the proteasome in NF-kB activation, the combining of conventional chemotherapy and radiation with proteasome inhibition, notably PS-341, new proteasome methods of inhibiting viral maturation, and the role of protesome inhibition in the treatment of AIDS. The authors also document the development of bortezomib (VelcadeTM) in Phase I clinical trials and in a multicentered Phase II clinical trials in patients with relapsed and refractory myeloma.

The book explores cutting-edge strategies to overcome proteasome inhibitor resistance, including the second generation 20S proteasome inhibitors, novel combinational therapies, and new targets in the ubiquitin-proteasome pathway (e.g., ubiquitin E3 ligases, deubiquitinases, 19S proteasomal ATPases, histone deacetylases, oxidative stress and proteotoxic stress pathways and pharmacogenomic signature profiling) in resistant cancer cells. The mechanisms of action and resistance of proteasome inhibitors, such as bortezomib and carfilzomib in human cancers, including multiple myeloma, mantle cell lymphoma, acute leukemia, and solid tumors are explored in depth in this volume. This timely volume unveils the most current discoveries of the mechanisms behind proteasome inhibitor resistance, which will help illuminate the future of cancer therapies.

Tyrosine Kinase Inhibitors as Sensitizing Agents for Chemotherapy, the fourth volume in the Cancer Sensitizing Agents for Chemotherapy Series, focuses on strategic combination therapies that involve a variety of tyrosine kinase inhibitors working together to overcome multi-drug resistance in cancer cells. The book discusses several tyrosine kinase inhibitors that have been used as sensitizing agents, such as EGFR, BCR-ABL, ALK and BRAF. In each chapter, readers will find comprehensive knowledge on the inhibitor and its action, including its biochemical, genetic, and molecular mechanisms' emphases. This book is a valuable source for oncologists, cancer researchers and those interested in applying new sensitizing agents to their research in clinical practice and in trials. - Summarizes the sensitizing role of some tyrosine kinase inhibitors in existing research - Brings recent findings in several cancer types, both experimental and clinically, with a particular emphases on underlying biochemical, genetic, and molecular mechanisms - Provides an updated and comprehensive knowledge regarding the field of combinational cancer treatment

Focusing on individual patient needs, Cancer Chemotherapy, Immunotherapy and Biotherapy: Principles and Practice, Seventh Edition, provides thorough, comprehensive information from Drs. Bruce A. Chabner, Dan L. Longo, and an authoritative team of clinicians and scientists working at renowned cancer centers across the globe. It covers fundamental information about mechanism of action, pharmacokinetics, clinical toxicity, and drug interactions, all essential to the safe and effective use of the drug.

This comprehensive monograph on the role of protein modulation in cancer therapeutics focuses on targeting molecules that regulate protein stability in a variety of tumors. Topics covered include ubiquitin ligases, deubiquitinating enzymes, and the proteasome.

A collection of cutting-edge techniques for studying ubiquitin-dependent protein degradation via the proteasome. The topics covered range broadly from basic biochemistry to cellular assays to discovery techniques using mass spectrometric analysis. These biochemical and cellular methods are necessary to explore the ubiquitin-proteasome system and ubiquitin-proteasome-dependent functions. State-of-the-art and user-friendly, Ubiquitin-Proteasome Protocols offers novice and experienced bench scientists alike a thorough compendium of readily reproducible techniques that will accelerate discovery, enhance productivity, and permit manipulation of the system for varied research purposes.

A Thorough Compilation of the Many Scientific Breakthroughs in the Ongoing Development of Precision Cancer Therapies Related to Lymphoma Targeting Oncogenic Drivers and Signaling Pathways in Lymphoid Malignancies: From Concept to Practice focuses on lymphoma, an area which has seen a remarkable number of breakthroughs in the ongoing development of precision cancer therapies. Each section on a specific biology or class of drugs has an introductory chapter written by an authority in the field, exclusively focused on the science and its relevance to cancer biology. This approach addresses the need for scientists, physicians, and the private sector to understand the broader context of the extraordinary advances that have produced such astonishing advances in the disease. The work primarily focuses on how to understand and translate fundamental principles of basic science into information that can be directly applied to patients – hence the subtitle, From Concept to Practice. To aid in readers’ comprehension, the first page of each chapter contains a box entitled ‘Take Home Points’. This short text will highlight the major unique points about the information contained within the chapter. Some of the key topics addressed in the work are as follows: Biological basis of the lymphoid malignancies: fundamental principles of lymphomagenesis and molecular classification of lymphoid malignancies Targeting programmed cell death: principles for understanding the many types of cell death and promising combinations of drugs targeting apoptosis Targeting the PI3K pathway: understanding the intricacies of this complex biology and precisely how targeted drugs can be leveraged therapeutically Targeting the cancer epigenome: pharmacologic features of drugs targeting the epigenome and future prospects for targeting various aspects of epigenetic control Targeting the tumour proteome: understanding the mechanisms of protein degradation in cancer including both older drugs like proteasome inhibitors, and newer PROTAC based approaches Written primarily for scientists and physicians in both the public and private sectors, Targeting Oncogenic Drivers and Signaling Pathways in Lymphoid Malignancies: From Concept to Practice is a comprehensive reference work for those interested in the growing area of Precision Cancer Therapies. Seamlessly integrating the basic and applied science, this volume will be an indispensable reference for those interested in translating the most important advances in science to innovative novel treatments for patients.

Therapeutic options for patients with myeloma have dramatically changed over the past 10 years. Beginning with the advances in therapy resulting from the use of high-dose therapy and autologous bone marrow or stem cell tra- plant, we have more than doubled the median survival for patients as a whole, and have now have a wealth of different biology -based treatment approaches for our patients in all disease stages. This book represents state-of-the-art information from many of the leaders in the plasma cell disorders world. Sections focusing on disease pathogenesis and biology, chemotherapy-based approaches, immune -based therapies, currently approved novel agents, developing targets, supportive care, and other plasma cell disorders provides a comprehensive collection and an excellent resource in this time of rapid change in clinical and preclinical disease knowledge. It is important to realize that these changes did not occur in a vacuum. Partnerships between academic institutions, the pharmaceutical industry, patient advocacy groups, the National Cancer Institute, community onco- gists, and ultimately our patients worked closely together to realize these advances, and to effect the radical changes in therapy we have witnessed over the past few years. This book would not have been possible without contri- tions from each of the gifted scientists and clinicians who worked tirelessly to prepare their individual chapters all the while maintaining commitment to the scientific and clinical mission of advancing care.

A comprehensive look at current drug discovery and development methods—and the roadmap for the future Providing both understanding and guidance in characterizing potential drugs and their production and synthesis, Development of Therapeutic Agents Handbook gives professionals a basic tool to facilitate research and development within this challenging process. This comprehensive text brings together, in one resource, a compendium of concepts, approaches, methodologies, and limitations that need to be considered in the formulation of therapeutic agents across a range of therapeutic fields. Both a reference and a call to action for the pharmaceutical industry, Development of Therapeutic Agents Handbook examines recent innovations taking shape in the various medical disciplines involved in drug discovery, and shows why these advances need to be embraced universally among researchers to improve their solution strategies. Additional subject matter includes: Extensive coverage and in-depth look into novel treatments and therapeutics Discussion of hot topics like new drugs and nutraceuticals, the discovery and development of vaccines, cancer therapeutics, and market overviews Coverage of therapeutic drug development for specific disease areas, such as cardiology, oncology, breast cancer, and kidney diseases As research in biology, chemistry, medicine, and technology rapidly progresses, it is becoming increasingly important for medical researchers to maintain an up-to-date knowledge base of emerging trends directing promising new therapies. Development of Therapeutic Agents Handbook serves this purpose, acting as both a one-stop reference rich in valid science, and a tool to carve out new pathways in the pursuit of bringing safer and more effective drugs to the marketplace.