Overcoming Cancers Resistant To Her 2 Antibodies

Overcoming Cancers Resistant to HER-2 Antibodies provides general updated information on the resistance of various human cancers to anti-HER2 therapeutic antibodies. It also discusses the description of various sensitizing agents that can reverse resistance when used in combination with anti-HER2 antibodies.There have been a lot of reports in which the treatment with anti-HER2 antibodies for various cancers has resulted in clinical responses; however, there have been also subsets of cancer patients who did not respond initially, and several responding patients developed resistance following treatments. Therefore, the use of various immunosensitizing agents to reverse resistance has been considered and this book discusses each of them in depth, such as Lapatinib, Ganetespib, Paclitaxel, Celecoxib, Emantasine, Liposomal Doxorubicin, and Kinase Inhibitors. This book is a valuable source for cancer researchers, oncologists, pharmacologists and different members of biomedical field interested in fighting cancer resistance to HER-2 antibodies. Provides a general summary of various sensitizing agents that can work effectively when used in combination with anti-HER2 antibodies to reverse resistance Offers potential underlying mechanisms by which the cancer cells are either inherently resistant or become unresponsive to antibody treatment Discusses how to develop new targeted agents to underlie resistance in order to expand research on this field

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.

​​​​The traditional approaches to treat various cancers include chemotherapy, radiation and/or hormonal therapy. While these therapies continue to be effective in large part, they are not selective and highly toxic. There have been encouraging results in alternative therapeutic approach called antibody-mediated anti-cancer therapy, which is less toxic, more selective, and can also reverse drug/radiation resistance. Monoclonal antibodies or mAbs can be used to destroy malignant tumor cells and prevent tumor growth by blocking specific cell receptors. mAbs can bind only to cancer cell-specific antigens and induce an immunological response against the target cancer cell. The book covers the common and unique features of mAbs agains various cancer, gives the latest developments on the molecular, biochemical and genetic mechanisms of resistance by various mAbs, as well as discuss novel mAbs to overcome resistance.

Resistance to Anti-CD20 Antibodies and Approaches for Their Reversal presents in-depth content written by international experts in the study of resistance to anti-CD20 antibodies and approaches for their reversal. Anti-CD20 antibodies are used to achieve B cell depletion and are developed to treat B cell proliferative disorders, including non-Hodgkin’s lymphoma and chronic lymphocytic leukemia. In the past two decades, anti-CD20 antibodies have revolutionized the treatment of all B cell malignancies, however, there are patients that fail to respond to initial therapy or relapse sooner. This book explores new and existing avenues surrounding Anti-CD20 antibodies. In recent years, several next-generation anti-CD20 therapies have been developed but predicting and reversing resistance is still a challenging task. These areas are being actively studied as they represent a potential to improve anti-CD20 therapies and are discussed thoroughly in the book. It is a valuable resource for researchers, students and member of the biomedical and medical fields who want to learn more about resistance to anti-CD20 antibodies and their reversal. • Presentation of current research, critical analyses, in-depth literature reviews, and the latest clinical reports on anti-CD20 antibody treatment • Discussion of recent developments of anti-CD20 antibodies in cancer and noncancer diseases treatment, possible resistance mechanisms and their reversals, as well as the exciting therapeutic opportunities offered by anti-CD20 antibodies in combination with chemotherapy or other treatment modalities • Utilization of a number of diagrams to visually illustrate complex content and plenty of tables to summarize important information

Multiple Myeloma remains an incurable malignancy. As the disease progresses, it invariably becomes resistant to treatment and almost all patients develop refractory disease. There are multiple different types of targeted therapies and many of them are used in combination at different stages of disease. Targeted therapies that are approved to be used include Proteasome Inhibitors, Immunomodulatory Drugs and Monoclonal Antibodies. Second and third generations of these drugs are developed to overcome resistance and they have unique mechanism of actions. Targeted therapies that are undergoing clinical trials include CAR-T cells, bi-specific antibodies, vaccines, ubiquitin ligase inhibitors and BCL-2 inhibitors. This book will help to develop an understanding of targeted therapies in Multiple Myeloma. Its goal is to provide a unique review of the mechanism of action and resistance of the many targeted therapies in Multiple Myeloma by leaders of the field. The book will be useful for students in medical science, clinicians, health professionals, scientists, pharmaceutical professionals, drug developers, and policy makers. This book will provide an insightful knowledge of the biology of Multiple Myeloma, the mechanism of action and resistance of targeted therapies, application of biomarkers and genomics and possible strategies in overcoming resistance and future development.

Gastrointestinal (GI) cancers, including gastric cancer, colon cancer, liver cancer, esophageal cancer, and pancreatic cancer, seriously threaten the health of human beings worldwide with a high rate of morbidity and mortality. The clinical successes achieved with immune checkpoint inhibitors (ICIs) targeting PD-1/PD-L1 and CTLA-4 have opened a new cancer therapy era and brought new hope to cancer patients. However, the overall response rate (ORR) of ICI monotherapy in the non-selective population is only about 20%, in which some patients subsequently develop immunotherapy resistance. Moreover, the remaining 70-80% of patients displayed primary resistance to ICIs, and a few patients even experienced hyper progression disease (HPD). Although PD-L1 expression, mismatch repair deficient (MMRd), high tumor mutational burden (TMB-H) , high homologous recombination deficiency (HRD), and tumor infiltrated immune cells (TILs) are known as effective biomarkers for immunotherapy, growing studies have reported that ICIs could not improve the OS of all patients with PD-L1 expression higher than 50%, and the ORR of MSI-H patients was only about 60%, whereas some patients with low PD-L1 expression or MSS could still benefit from immunotherapy, indicating the complexity of ICI resistance. Therefore, it is of great importance and significance to explore the prediction biomarkers for primary or acquired immunotherapy resistance and elucidate their underlying molecular mechanisms and develop reversal strategies. Due to the multiple steps of the cancer immune cycle and complex immune microenvironment, any disorders of immune cell infiltration or T cell activation, such as lack of antigens and/or their presentation, lack of response to antigen presentation, and T cell priming, could contribute to ICI resistance. The combination with anti-angiogenesis therapy, radiotherapy, chemotherapy, and other ICIs has improved the efficacy of ICI therapy to some extent in the clinic. Although numerous studies related to ICI resistance were reported in GI cancers, due to the strong spatial/temporal heterogeneity and the complex immune microenvironment in different kinds of GI cancers and different individuals, many questions about ICI resistance and reversal strategies remain unsolved. The aim of this Research Topic is to provide a forum to exhibit the latest research achievement related to the exploration of biomarkers for immunotherapy resistance including HPD and the underlying molecular mechanisms, as well as the development of reversal strategies in GI cancers. We hope this Research Topic will lead to a better understanding of precision cancer immunotherapy and provide useful clues for clinical application to benefit more GI cancer patients with immunotherapy.

Novel Sensitizing Agents for Therapeutic Anti-EGFR Antibodies presents a description of the sensitizers used to overcome resistance to anti-EGFR targeted antibody therapies in cancer, including novel engineered antibody drugs and other sensitizers. The book gives insights into the landscape of anti-EGFR based cancer treatments, the challenges of targeted therapy, and a glimpse into the future of antibody therapy. It offers pertinent science information on strategies used for the rational design and discovery of novel sensitizing agents, and in addition, translational studies involving pre-clinical and clinical design. This book is an indispensable resource for cancer researchers, medicinal chemists and other biomedical scientists.Finally, the book covers basic science strategies used in drug discovery and preclinical evaluation focused on EGFR blockage resistance, as well as clinical trial methodology, including clinical pharmacokinetics and imaging to address issues of efficacy evaluation of the new anticancer sensitizers for anti-EGFR drug resistance. Presents detailed descriptions on the history, chemistry, mechanism of action, structure-function relationships, pharmacology, side effects, dosing and formulation of new sensitizers to anti-EGFR antibodies Provides molecular structures for all novel anticancer drugs, along with strategies to overcome resistance to anti-EGFR antibodies Encompasses up-to-date information on the cancer drug discovery process, including new research tools, tumor-targeting strategies, and fundamental concepts in emerging areas of precision medicine