Clinical Therapeutic Development Against Cancers Resistant To Targeted Therapies

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 new volume updates the reader on selected areas of targeted therapy in breast cancer, with special emphasis on chemoprevention strategies, drug resistance, biomarkers, combination chemotherapy, angiogenesis inhibition and pharmacogenomics in the context of clinical efficacy. This selected review of targeted therapies will guide the reader on effective treatment as part of an integrated programme of patient management.

Targeted Therapy in Translational Cancer Research for the Translational Oncology series provides a comprehensive overview of recent developments in our understanding of tumor biology, elucidates the roles of targets and pathways involved in carcinogenesis, and describes current state-of-the-art anticancer therapy, as well as the most promising areas of translational research and targeted therapy. Introduces cutting-edge ‘bench to bedside and back’ breakthroughs which have transformed the diagnosis, prognosis, and treatment of cancer Covers basic principles of targeted therapy, including immunotherapy and the roles of cancer stem cells, the microenvironment, angiogenesis, epigenetics, microRNAs, and functional imaging in precision medicine Summarises major advances in therapeutic management of hematologic malignancies and solid tumors using conventional therapy, targeted therapy, immunotherapy, or novel treatment modalities

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.

​​​​​This volume gives the latest developments in on the mechanisms of cancer cell resistance to apoptotic stimuli, which eventually result in cancer progression and metastasis. One of the main challenges in cancer research is to develop new therapies to combat resistant tumors. The development of new effective therapies will be dependent on delineating the biochemical, molecular, and genetic mechanisms that regulate tumor cell resistance to cytotoxic drug-induced apoptosis. These mechanisms should reveal gene products that directly regulate resistance in order to develop new drugs that target these resistance factors and such new drugs may either be selective or common to various cancers. If successful, new drugs may not be toxic and may be used effectively in combination with subtoxic conventional drugs to achieve synergy and to reverse tumor cell resistance. The research developments presented in this book can be translated to produce better clinical responses to resistant tumors.

Over the past few decades, lymphoma patient outcomes have improved as a result of multidrug chemotherapy and radiation therapy, intensification of treatment, improvement in supportive care, and better imaging and staging systems. Even more recently, there has been tremendous progress in the understanding of cancer cell biology and its microenvironment which has resulted in the development of biologic agents, also called "target" therapies. These therapies are more specific in targeting cancer cells either directly or via enhancement of the immune system. Many clinical studies have focused on biological agents in combination with traditional chemotherapy with the goal of improved outcomes, or reduced acute long term complications that are associated with lymphoma therapy. This volume will review different classes of "target" drugs that have been developed, approved, or are under investigation in the field of lymphoma therapy. The discussion will not only be on the understanding of the mechanisms of action or clinical response of those agents, but will also help the reader to understand the nature of lymphoma biology in patients who relapse or are refractor after exposure to those drugs. Contributors will discuss what is currently known about mechanisms of tumor-related or host-related resistance, and how to overcome this resistance. This understanding is crucial given the dismal outcomes of patients with relapsed or refractory lymphomas. The book provides a unique opportunity to review and reflect on the recent successes and pitfalls of the modern lymphoma therapy era.

This book aims to educate nurses and advanced practice providers (APP’s) about known mutations, availability of targeted therapy and the management of patients with non-small cell lung cancer (NSCLC). It will educate nurses and practitioners about the scope of therapy to assure safe and effective lung cancer treatment. In this era of personalized medicine, nurses and APP’s are responsible for guiding patients from diagnosis through treatment. This starts with the identification of patients that can benefit from these therapies, the key role of biopsy acquisition (ie. what to test, when and how often) and treatment selection based on the mutation identified. Readers will learn about the mechanisms of action, administration, potential adverse side effects and unique management strategies for these targeted agents. Lung cancer continues to be the leading cause of cancer death in the United States and worldwide. Recent advances in the identification of specific oncogenic mutations that drive cancer development, growth and metastasis have led to major paradigm shifts in lung cancer treatment. Sophisticated methods are required to identify specific mutations at the time of diagnosis. This book explains how molecularly targeted therapies have been developed that target these drivers. To date, several tyrosine kinase inhibitors have been approved to target the epidermal growth factor receptor (EGFR), EML4-ALK ,ROS1 and BRAF. Most recently, immune checkpoint inhibitors have been approved with some indication that efficacy may be enhanced for patients who overexpress PD-L1. While some driver mutations have been identified, there is ongoing investigation into additional mutations. In the case of driver mutations, lung cancers will develop resistance to therapy. This book provides nurses and APP’s with the mechanisms of resistance that have been identified such as T790 mutation and many others in the EGFR mutation, and shows how the next level of drug development is focused on identifying mechanisms of resistance and development of new agents that overcome these mutations. With this book in hand, nurses and practitioners will be able to navigate patients through this ever expanding field of lung cancer treatment.