Protein Kinase Inhibitors As Sensitizing Agents For Chemotherapy

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

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. Presents cutting-edge agents and approaches with proved success in different model systems that can be translated to a different type of cancer Brings updated information to be used to propose new clinical trials investigating innovative strategies for improving responses to chemotherapy Provides mechanistic details to help guide the design of laboratory studies associated with clinical trials

Molecular Therapies of Cancer comprehensively covers the molecular mechanisms of anti-cancer drug actions in a comparably systematic fashion. While there is currently available a great deal of literature on anti-cancer drugs, books on the subject are often concoctions of invited review articles superficially connected to one another. There is a lack of comprehensive and systematic text on the topic of molecular therapies in cancer. A further deficit in the relevant literature is a progressive sub-specialization that typically limits textbooks on cancer drugs to cover either pharmacology or medicinal chemistry or signal transduction, rather than explaining molecular drug actions across all those areas; Molecular Therapies of Cancer fills this void. The book is divided into five sections: 1. Molecular Targeting of Cancer Cells; 2. Emerging and Alternative Treatment Modalities; 3. Molecular Targeting of Tumor-Host Interactions; 4. Anti-Cancer Drug Pharmacokinetics; and 5. Supportive Therapies.

Drug Efflux Pumps in Cancer Resistance Pathways: From Molecular Recognition and Characterization to Possible Inhibition Strategies in Chemotherapy, Volume Seven, describes the fundamental aspects of efflux pumps of the ATP-binding cassette superfamily in cancer resistance pathways, along with strategies to target and improve chemotherapy efficacy. Pumps of the ATP-binding cassette superfamily (ABCs) regulate the access of drugs to the intracellular space. In this context, the overexpression of ABCs is a well-known mechanism of multidrug resistance in cancer and is associated with therapeutic failure. Cancer types discussed include breast, endocrine, hematologic, gastrointestinal, musculoskeletal, lung, skin and central nervous system cancers. The book is a valuable source for researchers and advanced students in cancer, biology, pharmacology, pharmaceutical sciences, biomaterials and medical/clinical sciences that are interested in accessing a comprehensive compendium on efflux pumps in mechanisms of cancer resistance. Offers comprehensive and detailed descriptions of the basic aspects of efflux pumps in a very schematic and didactic manner Describes the involvement of efflux pumps in cancer resistance in different cancer types Encompasses an updated overview on state-of-the-art approaches that capitalize on their inhibition to improve chemotherapy and overcome resistance

pH Interfering Agents as Chemosensitizers In Cancer Therapy, Volume Thirteen, provides a detailed overview of the chemosensitizers for the treatment of cancer spanning from biochemical and structural features to pharmacology and drug-design, including technological applications. The book is structured with innovative outlines and a distinction between experimental and clinical results. The continuous discovery and assessment of the role played by old/new synthetic drugs, natural compounds and technological applications has led to the urgent need of classification in terms of biological activity, mechanism of action, clinical outcomes, cancer cell lines sensible to the treatment, and potentialities to better orient research in this field. Moreover, all the aspects relevant for medicinal chemistry (drug design, structure-activity relationships, permeability data, cytotoxicity, appropriate statistical procedures, and molecular modeling studies) are strictly considered. Presents a broad view of the topic according to a medicinal chemistry-based approach beyond syntheses and biological assays, focusing on SAR studies, chemoinformatic, drug targeting and molecular modeling Explains the mechanism of action of the chemosensitizers by means of schemes and figures to facilitate comprehension Discusses novel targets to explore new possibilities that enhance research in the field

Anti-angiogenic Drugs as Chemosensitizers in Cancer Therapy, Volume 19 focuses on the use of anti-angiogenic drugs as sensitizers of tumor cells to the inhibitory activity of antitumor agents. Conventional and novel anti-neoplastic agents (cytotoxic molecules, hormones/antihormones, immunotherapies) are taken into consideration, along with advances made in combination therapies. The book encompasses examples of studies on the use of antiangiogenic compounds—molecules that inhibit the growth of vessels inside a tumor—together with antineoplastic drugs in order to sensitize the resistant tumor to their cytotoxic effects, thus reducing adverse side reactions and resistance and improving the therapeutic response of cancer patients. In addition, the book discusses clinical applications in various types of cancer, such as colorectal, lung, breast, renal, genitourinary, skin and brain and circulating tumors. It is a valuable resource for cancer researchers, clinicians and members of the biomedical field who wants to be up-to-date on the most recent and promising developments in the field. Provides the most updated reviews on anti-angiogenic drugs as chemosensitizers by leaders in the field Encompasses summarized tables and schematic diagrams in each chapter to give a clear overview on recent findings in a didactic manner Brings not only relevant information of current research but also new ideas and suggestions for further investigations to help advance the field

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

Biological Mechanisms and the Advancing Approaches to Overcoming Cancer Drug Resistance, Volume 12, discusses new approaches that are being undertaken to counteract tumor plasticity, understand and tackle the interactions with the microenvironment, and disrupt the rewiring of malignant cells or bypass biological mechanism of resistance by using targeted radionuclide therapies. This book provides a unique opportunity to the reader to understand the fundamental causes of drug resistance and how different approaches are applied. It is a one-stop-shop to understand why it is so difficult to treat cancer, and why only a very few patients respond to therapy and a significant portion develop resistance. Despite a rapid development of more effective anti-cancer drugs and combination therapies, cancer remains the leading cause of lethality in the developed world. The main reason for this is the ability of heterogeneous subpopulations of tumor cells interacting with constantly evolving tumor microenvironment to resist elimination and eventually, trigger cancer relapse. In this book, experts review current concepts explaining molecular and biological mechanisms of cancer drug resistance and discussing advancing approaches for overcoming these therapeutic challenges. Provides the most updated knowledge on the mechanisms of cancer drug resistance and the emerging therapeutic approaches reviewed by experts in the field Brings detailed analyses of most important recently reported developments related to drug resistance and their relevance to overcoming it in cancer patients Discusses in-depth molecular mechanisms and novel concepts of cancer resistance to conventional and advanced therapies

Drug Repurposing in Cancer Therapy: Approaches and Applications provides comprehensive and updated information from experts in basic science research and clinical practice on how existing drugs can be repurposed for cancer treatment. The book summarizes successful stories that may assist researchers in the field to better design their studies for new repurposing projects. Sections discuss specific topics such as in silico prediction and high throughput screening of repurposed drugs, drug repurposing for overcoming chemoresistance and eradicating cancer stem cells, and clinical investigation on combination of repurposed drug and anticancer therapy. Cancer researchers, oncologists, pharmacologists and several members of biomedical field who are interested in learning more about the use of existing drugs for different purposes in cancer therapy will find this to be a valuable resource. Presents a systematic and up-to-date collection of the research underpinning the various drug repurposing approaches for a quick, but in-depth understanding on current trends in drug repurposing research Brings better understanding of the drug repurposing process in a holistic way, combining both basic and clinical sciences Encompasses a collection of successful stories of drug repurposing for cancer therapy in different cancer types

This is the first book to examine the future opportunities and challenges in the development of drugs which target kinases

Overcoming Ovarian Cancer Chemoresistance presents non-overlapping review chapters that discuss the state of the field in overcoming chemoresistance of ovarian cancer and treatment options before and following recurrence, considering the genetic makeup of the ovarian cancer patient and her tumor. With the uptake of both germline and somatic gene testing, clinicians can obtain a more comprehensive understanding of ovarian tumors and this book provides information to link the genetic makeup of a tumor (or patient) with the best available treatment. The book discusses topics such as strategies to fight chemo-resistance in ovarian cancer, circulating DNA as a monitor of response, BRCA mutations, ovarian cancer stem cells, immunotherapy and vaccines. Additionally, it brings a list of promising agents at clinical and pre-clinical stage that will impact the treatment in the near future. This book is a valuable source for cancer researchers, oncologists and several members of biomedical field who need to understand how to battle chemoresistance in ovarian cancer. Provides a comprehensive view of both biological and genetic determinants of resistance, as well as technical approaches to monitor response Discusses genetic reversions as a unique alteration and a new field of study Includes a chapter on upcoming and promising agents that are in the pre-clinical and early clinical space, to set the stage for future directions in the field

Therapeutic Strategies to Overcome ALK Resistance in Cancer, Volume 13, presents current strategies to improve and prolong clinical benefit in ALK driven cancers. Most patients with ALK-driven cancer are sensitive to tyrosine kinase inhibitor (TKI) therapy, but resistance invariably develops. This book discusses topics such as structure and function of ALK, ALK rearranged lung cancer, resistance mechanisms to ALK TKI tumors, and novel therapeutic strategies to enhance crizotinib anti-tumor efficacy in ALCL. Additionally, it encompasses information on drug combinations to enhance ALK TKI anti-tumor efficacy in neuroblastoma and future perspectives in the field. This book is a valuable resource for cancer researchers, clinicians and several members of biomedical field who need to understand more about how to fight ALK resistance in cancer treatment. Explains the biology of ALK RTK, focusing on its tissue expression, structure and functionality Presents an overview of current treatments and the benefits of ALK TKI in lung and other cancer types, such as ALCL, neuroblastoma and inflammatory myofibroblastic tumor Encompasses information on systemic treatments other than TKI, including chemotherapy, immunotherapy and antiangiogenic agents in ALK-driven NSCLC

In Breast Cancer Chemosensitivity, a group of world leading experts review critical aspects of resistance to systemic therapy in breast cancer patients. Beginning with a clinical overview of the problem, the book then focuses on the latest findings of molecular mechanisms of drug resistance. Coverage provides an example of using novel approaches for chemosensitization of breast cancer cells that gives readers an idea about the future direction in breast cancer treatment. It allows those who are interested in breast cancer therapy to get a jump-start on critical issues in breast cancer therapeutic resistance.

Overcoming Drug Resistance in Gynecologic Cancers provides up-to-date information related to important gynecologic cancers and focuses on mechanisms of drug resistance, genetics, signaling, immunology, health disparities, nanotechnology, economic considerations and financial impacts. The book covers not only drug resistance but also important means to reverse resistance both in the laboratory and clinic. The book discusses topics such as lifestyle, nutrition and risk of gynecologic cancers, the financial impact of drug resistance, chemosensitizing agents and targeted therapies in cervical, endometrial and ovarian cancer, immunotherapy to overcome drug resistance, and genetic polymorphisms in gynecologic cancers. Additionally, it discusses ethnic and racial health disparity perspectives and future developments in chemosensitizing activities to reverse drug resistance in gynecologic cancers. It is a valuable resource for cancer researchers, oncologists, clinicians and other biomedical field members who are interested in new approaches to improve chemotherapy outcome in patients with gynecologic cancers. Provides a comprehensive resource with all the details needed for readers to understand and follow information Encompasses schematics, diagrams and flow charts in all chapters to help readers easily follow critical information Presents tables and figures especially developed to summarize the information with appropriate statistical rigor and to show details of clinical specimens such as pathological, radiological characteristics, and/or laboratory biomarkers

New Targeting in The Reversal of Resistant Glioblastomas discusses alternative treatment strategies that not only target tumor cells but also target the tumor microenvironment, metabolic pathways and interaction of cytokines in tumor cells. The current treatment for primary and recurrent glioblastomas is failing because clinicians are not considering the effect of bone marrow derived cells to the development of resistance to clinically practiced therapies. This book helps readers rethink treatment strategies to successfully fight glioblastomas. It is a valuable resource for cancer researchers, clinicians, graduate students and other members of the biomedical field. Explains the effect of bone marrow derived cells on the development of resistance to clinically practiced therapies Provides information on the availability of alternate therapies for recurrent glioblastoma when standard practices have failed Discusses targeting tumor microenvironment using available FDA approved drugs as an alternative treatment strategy for glioblastoma