This book will be a guide to understanding resistance against targeted therapeutic approaches for cancer using immunotoxins. It contains a detailed review of the history and development of targeted therapy. As well, it includes an in-depth description of the molecular and cellular mechanisms involved in cancer resistance and several novel methods to overcome resistance. Each chapter discusses different aspects of resistance and covers all the factors that may contribute to resistance in cancer cells. Finally, this volume highlights the recent findings and advances associated with tackling cancer resistance.

Nitric Oxide (NO) is a pleitropic, ubiquitous modulator of cellular functions. Aryl nitrite and glyceryl trinitrate, representative intravasadilators, were introduced as therapeutic agents more than a century ago for relief from acute attacks of angina. The vasodilator action is mediated by the release of NO following treatment. NO has important therapeutic applications in several diseases such as inflammatory diseases, erectile dysfunction, inflammation, pain and neural protective activity. However, the role of NO in cancer and its application in therapy has received little attention. This monograph will be the first to focus on studies that investigate the role of NO in tumor cell pathogenesis, growth, angiogenesis, response to cytotoxic therapies and NO translational applications in cancer therapy, alone or in conjunction with other therapies.

Advances in Nitric Oxide and Cancer is a volume that serves to give the latest research on nitric oxide (NO) and cancer. More specifically, the volume reviews significant advances in the application of NO-mediated drugs. The volume explores nitric oxide and its relationship to cancer spanning from its roles in the pathogenesis, prognosis, gene and protein modifications, regulation of resistance to cytotoxics, and therapeutic applications. With chapters written by leading experts, the volume addresses the burgeoning interest in a rapidly advancing field and provides a valuable resource to scientists who have initiated research as well as clinical investigations in their laboratories on the various roles of NO and cancer.

This comprehensive volume explores the latest research on the mechanisms of resistance in cancer cells to CTL-mediated immunotherapy. Chapter topics discuss cell-mediated immunity as the result of cytotoxic T-lymphocytes (CTL) directed specifically against cancer cells. In addition, the volume reviews how CTL mediate the cytotoxic activity, in large part, by the indication of apoptosis; hence, tumor cells develop anti-apoptotic mechanisms and thereby, resist CTL-induced apoptosis. In order for CTL-mediated antitumor immunotherapy to be effective, it is essential that agents directed against the resistant tumor cells sensitized cancer cells for CTL-mediated apoptosis. Examples of such agents discussed in the volume include are HDAC inhibitors, proteasome inhibitors, Bcl-2 family inhibitors, PARP, antibodies, and more.

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.

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.

This book reviews novel approaches developed to reverse tumor cell resistance to chemo/immuno/radio-therapy and the use of various sensitizing agents in combination with various cytotoxics. It also introduces several current approaches developed by established investigators that are aimed at overcoming resistance. This is the first volume to compile studies on tumor cell sensitization. It will prove useful for students, scientists, clinicians and pharmaceutical companies.

This book will be a guide to understanding resistance against targeted therapeutic approaches for cancer using immunotoxins. It contains a detailed review of the history and development of targeted therapy. As well, it includes an in-depth description of the molecular and cellular mechanisms involved in cancer resistance and several novel methods to overcome resistance. Each chapter discusses different aspects of resistance and covers all the factors that may contribute to resistance in cancer cells. Finally, this volume highlights the recent findings and advances associated with tackling cancer resistance.

Advances in Nitric Oxide and Cancer is a volume that serves to give the latest research on nitric oxide (NO) and cancer. More specifically, the volume reviews significant advances in the application of NO-mediated drugs. The volume explores nitric oxide and its relationship to cancer spanning from its roles in the pathogenesis, prognosis, gene and protein modifications, regulation of resistance to cytotoxics, and therapeutic applications. With chapters written by leading experts, the volume addresses the burgeoning interest in a rapidly advancing field and provides a valuable resource to scientists who have initiated research as well as clinical investigations in their laboratories on the various roles of NO and cancer.

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.

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.

This book reviews novel approaches developed to reverse tumor cell resistance to chemo/immuno/radio-therapy and the use of various sensitizing agents in combination with various cytotoxics. It also introduces several current approaches developed by established investigators that are aimed at overcoming resistance. This is the first volume to compile studies on tumor cell sensitization. It will prove useful for students, scientists, clinicians and pharmaceutical companies.

Role of Nutraceuticals in Chemoresistance to Cancer, Volume Two, focuses on nutraceuticals, the compounds derived from natural sources, which are usually multi-targeted as a means to overcome chemoresistance. This book discusses the role of several compounds related to nutraceuticals and chemoresistance, such as curcumin, resveratrol, indole 3-carbinol, tocotrienols, ursolic acid, fisetin, celastrol, gambogic, butein, catechins and silymarin. It is a valuable resource for cancer researchers, oncologists and members of several areas of the biomedical field who are interested in understanding how to use nutraceuticals as a sensitizing agent for chemotherapy.

Nitric Oxide as a Chemosensitizing Agent, Volume One is the first book to describe several reviews by authoritative scientists and clinicians on novel findings in the reversal of drug resistant cancers by the combination treatment of Nitric Oxide and sub toxic concentrations of chemotherapeutic drugs that have been reported in both in vitro, in vivo and preclinical models. The book describes the various underlying chemical, molecular and genetic mechanisms by which NO and NO reactive species mediate the anti-cancer activity, thus reducing the threshold of drug resistance and enabling chemo therapeutic drugs to induce their cytotoxic activity and reversal of resistance. This book exposes scientists and clinicians to this highly beneficial topic for research investigations and pharmaceutical companies to new avenues for R&D. It is a valuable resource for cancer researchers, oncologists and members of several areas of the biomedical field who are interested in understanding how to use Nitric Oxide as a sensitizing agent for chemotherapy.

Targeting Cell Survival Pathways to Enhance Response to Chemotherapy encompasses recently developed molecular targeting agents and approaches that suppress cell survival signaling. Cell survival signaling attenuates the effectiveness of conventional chemotherapy and numerous mechanisms have been described, and continue to be described, which contribute to cell survival in the face of chemotherapy treatment. Key pathways leading to chemoresistance emanate from growth factor receptors, PI3K, STAT3, anti-apoptotic Bcl-2 family members, autophagy, and the DNA damage response pathway. New advances have underscored the potential of targeting each of these cell survival mechanisms to improve responsiveness to chemotherapy. This book reviews these recent advances and provides a foundational background and hints of new opportunities for basic, translational, and clinical investigators focused on improving therapeutic responses to chemotherapy.

Nitric Oxide (NO) is a pleitropic, ubiquitous modulator of cellular functions. Aryl nitrite and glyceryl trinitrate, representative intravasadilators, were introduced as therapeutic agents more than a century ago for relief from acute attacks of angina. The vasodilator action is mediated by the release of NO following treatment. NO has important therapeutic applications in several diseases such as inflammatory diseases, erectile dysfunction, inflammation, pain and neural protective activity. However, the role of NO in cancer and its application in therapy has received little attention. This monograph will be the first to focus on studies that investigate the role of NO in tumor cell pathogenesis, growth, angiogenesis, response to cytotoxic therapies and NO translational applications in cancer therapy, alone or in conjunction with other therapies.

Successes and Challenges of NK Immunotherapy: Increasing Anti-tumor Efficacy describes the unique therapeutic applications of NK cells to fight cancers and eliminate the bulk and subset of cancer stem cells responsible for metastasis, relapse and recurrences. The book provides information on the development, engineering, mechanisms of action, response to various preclinical models, and applications in various clinical trials. Sections cover the development of highly engineered cytotoxic NK cells, their mechanisms of action, preclinical and clinical applications, the development and application of CAR-NK cells, and new NK-drug conjugates, also emphasizing that activated NK cells can target and kill highly resistant cancer stem cells. Written by the leading experts on NK immunotherapy worldwide, this is a valuable resource for researchers, clinicians and members of the biomedical field who are interested in understanding novel and efficient therapies to fight cancers.

YY1 Is Pivotal in the Control of the Pathogenesis and Drug Resistance of Cancer: A Critical Therapeutic Target describes the current state-of-the-art of the transcription factor YY1 that is overexpressed in the majority of cancers and a central factor that regulates all of the major features and characteristics of human cancers. This book emphasizes the biochemical, molecular and genetic underlying mechanisms by which YY1 regulates its pro-cancerous activities. In addition, it also describes the role of YY1 in the regulation of tumor cell resistance to conventional chemo and immunotherapies and the important role of inhibiting YY1 in cancer. This book is a valuable source for cancer researchers, oncologists and several members of medical and biomedical field who are interested in understanding further the role of YY1 in cancer.

Prognostic and Therapeutic Applications of RKIP in Cancer provides updated reviews on the chemistry, signaling, pre-clinical and clinical activities, and role of RKIP expression levels for diagnostics, prognosis and potential interventions. The development of novel compounds and conjugates that selectively induce RKIP expression in cancer open a novel era of new therapeutics and their potential in the treatment of highly resistant cancers and metastases. Edited and written by internationally renowned experts in the field of novel therapeutics for cancer, this book is a valuable source for cancer researchers, medical scientists, clinicians, clinical pharmacologists, and graduate students.

Improving the Therapeutic Ratio in Head and Neck Cancer provides a complete review of current approaches to modulating therapeutic sensitivity in head and neck cancer. It presents a broad background of current approaches and by highlighting the potential for clinical translational, introduces a roadmap for how to move promising preclinical findings into the clinic. The book discusses topics such as immunotherapy and molecularly targeted therapies in head and neck cancer, PI3k/mTOR pathway, autophagy inhibition to sensitize HNC to radiation and chemotherapy, TAM and Eph/Ephrin family proteins and metabolic reprogramming to modulate therapeutic sensitivity. Additionally, it details approaches to improve the response to immunotherapy, and Chk1/2 inhibition in radiation and cetuximab resistance. This book is a valuable source to head and neck cancer researchers and advanced students, and to those studying specific approaches in other model systems and disease sites.

Breaking Tolerance to Pancreatic Cancer Unresponsiveness to Chemotherapy edited by Dr. Nagaraju, PhD., DSc. focuses on overriding the resistance from chemotherapeutic drugs with a broader range of treatment options. It particularly focuses on stroma, tumor microenvironment, stem cells, stellate cells, transcription factors, growth factors, and important signaling pathways. This volume discusses topics such as pancreatic cancer biology, current therapeutic options, EMT, chemotherapy resistance mechanisms, and genetic manipulations and natural products to enhance the sensitivity of pancreatic cancer to chemotherapy. Additionally, it discusses small targeted molecules and pancreatic cancer trials, and nanotechnology-based drug delivery. Breaking Tolerance to Pancreatic Cancer Unresponsiveness to Chemotherapy is a valuable source for researchers and advanced students in cancer and oncology as well as clinicians and medical students who are interested in learning more about ways to break pancreatic cancer resistance to chemotherapy.

Therapeutic Application of Nitric Oxide in Cancer and Inflammatory Disorders presents updated reviews on the chemistry, signaling, pre-clinical and clinical activities on the role of nitric oxide donors/inhibitors used alone and in combination with other therapeutic agents for the treatment of a variety of diseases. This book examines various studies related to the application of novel therapeutic NO (donors/inhibitors) compounds in the treatment of various cancers. These studies have been shown to exert significant therapeutic activities against various cancers and various inflammatory diseases such as rheumatoid arthritis, Crohn's disease, allergies, and asthma, where no current effective therapies exist. Pathologies based on functional and structural vascular alterations are also taken into consideration. Edited and written by internationally renowned experts in the field of novel therapeutics for cancer, this book is a valuable source for cancer researchers, medical scientists, clinicians, clinical pharmacologists, and graduate students.

Overcoming Cancers Resistant to HER-2 Antibodies provides general updated information on the resistance of various human cancers to anti-HER2 therapeutic antibodies. The book 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. Sections cover 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 the biomedical field interested in fighting cancer resistance to HER-2 antibodies.