Glioblastoma Resistance to Chemotherapy: Molecular Mechanisms and Innovative Reversal Strategies

Glioblastoma Resistance to Chemotherapy: Molecular Mechanisms and Innovative Reversal Strategies brings current knowledge from an international team of experts on the science and clinical management of glioblastoma chemoresistance. The book discusses topics such as molecular mechanisms of chemoresistance, experimental models to study chemoresistance, chemoresistance to drugs other than Temozolomide, and specific strategies to reverse chemoresistance. Additionally, it encompasses information on how to mitigate chemoresistance by targeted enhancement of p53 function. This book is a valuable resource for cancer researchers, oncologists, neuro-oncologists and other members of the biomedical field. Glioblastoma (GBM) is the most invasive and malignant primary brain tumor in humans with poor survival after diagnosis, therefore it is imperative that molecular and cellular mechanisms behind therapy resistant GBM cells, as well as the therapeutic strategies available to counter the resistance are comprehensively understood. Provides comprehensive, core knowledge related to the entire discipline of glioblastoma chemoresistance, from its many etiological mechanisms, to specific strategies to reverse resistance Presents current information from an international team of experts on the basic science, pre-clinical research, and clinical management of glioblastoma chemoresistance Discusses molecular and cellular mechanisms behind therapy resistant glioblastoma cells, as well as the therapeutic strategies available to counter this 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.

With chapters from highly skilled, experienced, and renowned scientists and researchers from around the globe, Dendrimers for Drug Delivery provides an abundance of information on dendrimers and their applications in the field of drug delivery. The volume begins with an introduction to dendrimers, summarizing dendrimer applications and the striking features of dendrimers. It goes on to present the details of usual properties, structure, classification, and methods of synthesis, with relevant examples. The toxicity of dendrimers is also discussed. The chapter authors provide an exhaustive amount of information about dendrimers and their biomedical applications, including biocompatibility and toxicity aspects, a very useful feature. This informative volume will be valuable resource that will help readers to create products derived from dendrimers and navigate through the regulatory, manufacturing, and quality control hurdles. It will be an important resource for researchers, scientists, upper-level students, and industry professionals.

Nullius in verba. . . Truth will be tested not by words. Horace (Epistles) Few read introductions except for book reviewers, who want to take a shortcut and avoid reading the book itself. However, tradition requires that the preface make public why the book was written at all (this is not supposed to include powerful reasons such as augmenting the ego of the editor and authors). Frequently, the inflationary tendency to publish in verbose length is in conflict with market forces and interest. No doubt, multidrug resistance is a "fashionable" topic, but there are many fashions displayed on the cat-walk of scientific literature. One can rationalize that the forces driving our concern with multi drug resistance reflect the frustration of pharmaceutical companies and oncologists alike: as soon as a new anticancer drug enters clinical trials, cancer cells start eluding extinction with their elaborate and successful mechanisms. Many grants have been awarded and spent, only to confirm the futility of our efforts to defeat this cellular Darwinism. Our medical and scientific training makes it hard, if not impossible, to accept that the survival of a malignant cell, alone or as part of a tissue, is part of the continuance of life. Since exposure to noxious and lethal substances is unavoidable, cells have been forced to develop a multitude of mechanisms to prevent entry or accelerate exit of such materials from intracellular space.

Leading experts summarize and synthesize the latest discoveries concerning the changes that occur in tumor cells as they develop resistance to anticancer drugs, and suggest new approaches to preventing and overcoming it. The authors review physiological resistance based upon tumor architecture, cellular resistance based on drug transport, epigenetic changes that neutralize or bypass drug cytotoxicity, and genetic changes that alter drug target molecules by decreasing or eliminating drug binding and efficacy. Highlights include new insights into resistance to antiangiogenic therapies, oncogenes and tumor suppressor genes in therapeutic resistance, cancer stem cells, and the development of more effective therapies. There are also new findings on tumor immune escape mechanisms, gene amplification in drug resistance, the molecular determinants of multidrug resistance, and resistance to taxanes and Herceptin.

Treatment of glioma is currently one of the most challenging problems in oncology, as well as in neurosurgery. Despite major advances in our understanding of the pathomechanism, diagnosis by imaging and the availability of powerful therapeutic tools, the life expectancy of patients with glioblastoma has only been slightly prolonged and a cure remains elusive. None of the currently available surgical tools, including operative microscopes, lasers and image-guided surgery, can enable the detection and removal of all of the tumor tissue. In recent years, however, the landscape has been changing immeasurably, and molecular studies over the past two decades have identified a variety of genetic aberrations that are specifically associated with individual types of gliomas. In addition, certain molecular abnormalities have been linked to therapy responses, thereby establishing clinical biomarkers and molecular targets, and the use of novel agents is being investigated. These agents have been specifically engineered to exert specific cytotoxicity against gliomas, either on their own as single agents or in combination with other modalities. Moreover, there has been an enormous surge of interest in the area of immunology and immunotherapy, which has been facilitated by our understanding of the molecular basis of gliomas. Although several kinds of immunotherapeutic trials have been undertaken, we still await a great breakthrough in terms of clinical efficacy to prolong the survival time of glioma patients.

In spite of the development of various anticancer drugs, the therapy of cancer has remained challenging for decades. The current therapy of cancer is overwhelmed because of the inability to deliver therapeutics to all regions of a tumor in effective therapeutic concentrations, intrinsic or acquired resistance to the treatment with currently available agents via genetic and epigenetic mechanisms, and toxicity. As a result, cancer therapy using conventional therapeutics and different types of treatment regimens using this therapeutics has not led to a convincing survival benefit of the patients. In this context, Macromolecular therapeutics offer several advantages over conventional low molecular therapeutics by various ways such as, enable the use of larger doses of these agents by limiting the toxicity, by enhanced permeability and retention into tumors, by tumor targeting using tumor-specific antibodies, by specific inhibition of oncogenes using anticancer oligonucleotides etc. Cancer treatment using this macromolecular therapeutics has considerably improved the survival benefit for patients. As a result, various macromolecular therapeutics are already commercialized or are under clinical development. Although we are far from a real magic bullet today, looking at the pace of research and current success in this field of macromolecular therapeutics, it appears that we are approaching a magic bullet for the efficient treatment of cancer. Thus, we believe that the subject of this book is very timely, and that the book will fill an unmet need in the market. This book is unique and assembles various types and aspects of macromolecular anticancer therapeutics for cancer therapy in one shell and conveys the importance of this interdisciplinary field to the broad audience. Thus, in a nutshell, this book details the basics of cancer, and various therapeutic strategies such as those based on macromolecular therapeutics hence can become an important reference for practitioners, oncologists, medical pharmacologists, medicinal chemists, biomedical scientists, experimental pharmacologists, pharmaceutical technologists, and particularly it can essentially become a handbook of macromolecular therapeutics for cancer therapy for graduates, post-graduates and Ph.D. students in these fields.

Cancer Treatment: Conventional and Innovative Approaches is an attempt to integrate into a book volume the various aspects of cancer treatment, compiling comprehensive reviews written by an international team of experts in the field. The volume is presented in six sections: i) Section 1: Cancer treatment: Conventional and innovative pharmacological approaches; ii) Section 2: Combinatorial strategies to fight cancer: Surgery, radiotherapy, backytherapy, chemotherapy, and hyperthermia; iii) Section 3: The immunotherapy of cancer; iv) Section 4: Multidisciplinarity in cancer therapy: nutrition and beyond; v) Section 5: Supportive care for cancer patients; vi) Section 6: Perspectives in cancer biology and modeling. Ultimately, we hope this book can enlighten important issues involved in the management of cancer, summarizing the state-of-the-art knowledge regarding the disease control and treatment; thus, providing means to improve the overall care of patients that daily battle against this potentially lethal condition.

This second edition comes at a time of a paradigm shift in understanding of the molecular pathology and neuroscience of brain and spinal tumors of childhood and their mechanisms of growth within the developing brain. Excellent collaborative translational networks of researchers are starting to drive change in clinical practise through the need to test many ideas in trials and scientific initiatives. This text reflects the growing concern to understand the impact of the tumour and its treatment upon the full functioning of the child’s developing brain and to integrate the judgments of the risks of acquiring brain damage with the risk of death and the consequences for the quality of life for those who survive. Information on the principles of treatment has been thoroughly updated. A chapter also records the extraordinary work done by advocates. All medical and allied professionals involved in any aspect of the clinical care of these patients will find this book an invaluable resource.

This book focuses on the prophylactic potential of diet-derived factors in primary prevention of cancer. It is written by a group of highly reputed experts in the area of dietary agents and cancer chemoprevention. The translational potential of dietary factors from epidemiological, laboratory and clinical studies as prevention strategy in normal and risk populations is highlighted. The work presents options of routine inclusion of specific dietary regimens for prevention as well as therapeutic strategy for better management through adjuvant interventions in cancer treatment.

This timely book, published just as cancer immunotherapy comes of age, summarizes the rationale, present status, and future perspective for cancer immunotherapy. Included are explanations of the constitution of the immune system and immunocheckpoints, the mechanism of antigen presentation and recognition, valuable modalities, clinical trials and guidance, personalization, and biomarkers, all of which are essential for understanding the success of cancer immunotherapy. This innovative therapy has been investigated worldwide as the fourth line of cancer treatment after the standard treatments of surgery, chemotherapy, and radiotherapy. The progress in fundamental understanding of tumor immunology and the recent advances in clinical trials have opened new avenues with a cancer vaccine in 2010 and immunocheckpoint modulation in 2011, with their approval already granted in the United States. Today, there are no doubts, even among experts in cancer chemotherapy and radiotherapy, that the immune system plays a vital role in tumor eradication. Following American approval, many clinical trials of cancer immunotherapy are being conducted. With this book the reader will readily understand the paradigm shift in cancer treatment and will realize the importance of cancer immunotherapy. The great value of immunotherapy will be obvious, not only for tumor shrinkage but for prolonging patient survival.

PARP Inhibitors for Cancer Therapy provides a comprehensive overview of the role of PARP in cancer therapy. The volume covers the history of the discovery of PARP (poly ADP ribose polymerase) and its role in DNA repair. In addition, a description of discovery of the PARP family, and other DNA maintenance-associated PARPs will also be discussed. The volume also features a section on accessible chemistry behind the development of inhibitors. PARP inhibitors are a group of pharmacological inhibitors that are a particularly good target for cancer therapy. PARP plays a pivotal role in DNA repair and may contribute to the therapeutic resistance to DNA damaging agents used to treat cancer. Researchers have learned a tremendous amount about the biology of PARP and how tumour-specific defects in DNA repair can be exploited by PARPi. The “synthetic lethality” of PARPi is an exciting concept for cancer therapy and has led to a heightened activity in this area.

A complete introduction and guide to the latest developments in cancer gene therapy-from bench to bedside. The authors comprehensively review the anticancer genes and gene delivery methods currently available for cancer gene therapy, including the transfer of genetic material into the cancer cells, stimulation of the immune system to recognize and eliminate cancer cells, and the targeting of the nonmalignant stromal cells that support their growth. They also thoroughly examine the advantages and limitations of the different therapies and detail strategies to overcome obstacles to their clinical implementation. Topics of special interest include vector-targeting techniques, the lessons learned to date from clinical trials of cancer gene therapy, and the regulatory guidelines for future trials. Noninvasive techniques to monitor the extent of gene transfer and disease regression during the course of treatment are also discussed.

Second Generation Cell and Gene-Based Therapies: Biological Advances, Clinical Outcomes, and Strategies for Capitalisation serves as the only volume to the market to bridge basic science, clinical therapy, technology development, and business in the field of cellular therapy/cytotherapy. After more than two decades of painstaking fundamental research, the concept of therapeutic cells (stem cells, genes, etc.), beyond the concept of vaccines, is reaching clinical trial, with mounting confidence in the safety and efficacy of these products. Nonetheless, numerous incremental technical advances remain to be achieved. Thus, this volume highlights the possible R&D paths, which will ultimately facilitate clinical delivery of cutting edge curative products. The next waves of innovation are reviewed in depth for hematopoietic stem cells, mesenchymal stem cells, tissue engineering, CAR-T cells, and cells of the immune system, as well as for enabling technologies such as gene and genome editing. Additionally, deep dives in product fundamentals, history of science, pathobiology of diseases, scientific and technological bases, and financing and technology adoption constraints are taken to unravel what will shape the cytotherapy industry to the horizon 2025 and beyond. The outcome is not simply a scientific book, but a global perspective on the nascent field combining science, business, and strategic fundamentals. Helps readers learn about the most current trends in cell-based therapy, their overall effectiveness from a clinical prospective, and how the industry is moving therapies forward for capitalization "Perspectives" section at the end of each chapter summarizes key learnings, hypotheses, and objectives highlighted and combines scientific and business insights Edited and authored by scientists representing both basic and clinical research and industry, presenting a complete story of the current state and future promise of cellular therapies

This volume presents the entire breadth of translational cancer research and brings together members of academia and industry in the expectation of accelerating interactions and progress in the field. A variety of key topics are presented, beginning with discovery of molecular targets and pathways (oncogene, cell survival, tumor suppression, cell death), host-neoplasm interactions (cell adhesion, matrix proteases), early detection, monitoring progression, understanding tumor progression and metastasis, immune surveillance, in vivo molecular imaging, animal models, drug discovery including chemistry, high-throughput assays, mechanism determination, target validation, therapeutic window and some progress in clinical trials for more advanced agents and targets.

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 book discusses cancers and the resurgence of public interest in plant-based and herbal drugs. It also describes ways of obtaining anti-cancer drugs from plants and improving their production using biotechnological techniques. It presents methods such as cell culture, shoot and root culture, hairy root culture, purification of plant raw materials, genetic engineering, optimization of culture conditions as well as metabolic engineering with examples of successes like taxol, shikonin, ingenol mebutate and podophylotoxin. In addition, it describes the applications and limitations of large-scale production of anti-cancer compounds using biotechnological means. Lastly, it discusses future economical and eco-friendly strategies for obtaining anti-cancer compounds using biotechnology.

The tumor microenvironment has become a very important and hot topic in cancer research within the past few years. The tumor microenvironment is defined as the normal cells, molecules, and blood vessels that surround and feed a tumor cell. As many scientists have realized, studying the tumor microenvironment has become critical to moving the field forward, since there are many players in a tumor’s localized and surrounding area, which can significantly change cancer cell behavior. There is a dual relationship wherein the tumor can change its microenvironment and the microenvironment can affect how a tumor grows and spreads. Tumor Microenvironment in Cancer Progression and Cancer Therapy aims to shed light on the mechanisms, factors, and mediators that are involved in the cancer cell environment. Recent studies have demonstrated that in addition to promoting tumor progression and protecting tumor cells from the spontaneous immune-mediated rejection and different forms of cancer therapeutics, tumor microenvironment can also be a target and mediator of both standard and newly-emerging forms of cancer therapeutics. Thus, the dual role of the tumor microenvironment is the integral focus of the volume. The volume highlights the bi-directional interactions between tumor cells and non-malignant tumor component during tumor progression and treatment. It also focuses on the three groups of the reactive tumor component: stromal cells, blood vessels and the infiltrating immune cells. These three groups are discussed under the lens of their role in promoting tumor growth, shielding the tumor from rejection and from standard forms of cancer therapies. They are emerging as targets and mediators of standard and new forms of potential therapy.