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Oligonucleotides as Therapeutic Agents
The use of oligonucleotides as therapeutic agents rests upon their ability to interfere, in a sequence-specific manner, with the fundamental machinery of protein synthesis either by binding to the mRNAs transcribed from a gene or by binding directly to a target gene. This approach can be used not only for inhibition of the synthesis of host proteins but also of those required by invading pathogens. Potential therapeutic applications are enormous, ranging over hypertension, cardiovascular disease, autoimmune disease, vital and other parasitic infections (especially HIV), and cancer. This book discusses the chemistry and pharmacokinetics of oligonucleotides and their analogues, and surveys the results of structure-activity studies and current clinical trials. It also critically reviews the problems with antisense therapy, such as the enzymatic destruction of oligonucleotides, the doses required for a therapeutic response, the difficulty in directing oligonucleotides to particular target tissues and cells, the need for parenteral administration, and doubts concerning the mechanism of action (especially problems associated with non-specific binding to proteins) and long-term effects.
Antiangiogenic Agents in Cancer Therapy
This volume represents a compendium of scientific findings and approaches to the study of angiogenesis in cancer. The second edition of Antiangiogenic Agents in Cancer Therapy is intended to give a current perspective on the state-of-the-art of angiogenensis and therapy directed at this process. Antiangiogenesis is a dynamic and evolving field in oncology. New therapeutic targets continue to emerge followed by the rapid development of new therapeutic agents to be investigated in clinical trials. Optimizing the therapeutic potential of antiangiogenic agents in combination with the other therapies in the armamentarium to fight cancer will be an on-going challenge.
Transforming Growth Factor-Beta in Cancer Therapy, Volume II
Transforming Growth Factor- ß in Cancer Therapy, Vols. 1 and 2, provides a compendium of findings about the role of transforming growth factor- ß (TGF- ß) in cancer treatment and therapy. The second volume, Cancer Treatment in Therapy, is divided into three parts. The companion volume details the role of TGF- ß on basic and clinical biology.
Transforming Growth Factor-Beta in Cancer Therapy, Volume I
Transforming Growth Factor- ß in Cancer Therapy, Vols. 1 and 2, provides a compendium of findings about the role of transforming growth factor- ß (TGF- ß) in cancer treatment and therapy. The first volume, Basic and Clinical Biology, is divided into three parts. This volume’s companion, Cancer Treatment in Therapy, examines transforming growth factor- ß in other developing and advanced cancers and methods of treatment and therapy.
Death Receptors in Cancer Therapy
An in depth review of our latest understanding of the molecular events that regulate cell death and those molecules that provide targets for developing agonists or antagonists to modulate death signaling for therapeutic purposes. The authors focus on the extrinsic system of death receptors, their regulation and function, and their abnormalities in cancer. Topics of particular interest include resistance to apoptosis, TRAIL signaling, death receptors in embryonic development, mechanisms of caspase activation, and death receptor mutations in cancer. Additional chapters address death signaling in melanoma, synthetic retinoids and death receptors, the role of p53 in death receptor regulation, immune suppression of cancer, and combination therapy with death ligands.
Hematopoietic Growth Factors in Oncology
Whether to promote platelet recovery or to ameliorate the complications of cancer and the side effects of chemotherapy, hematopoietic growth factors (HGFs) now account for more than $5 billion per year of the US health care budget. In Hematopoietic Growth Factors in Oncology: Basic Science and Clinical Therapeutics, leading oncologists, hematologists, and nephrologists comprehensively review the role of HGFs in clinical practice, explain the molecular basis of their effects, and consider potential future developments. The authors focus on the use of HGFs in oncology, describing their cutting-edge application to patients with lung cancer, Hodgkin's and non-Hodgkin's lymphoma, breast cancer, c...
Histone Deacetylases
A panel of leading investigators summarizes and synthesizes the new discoveries in the rapidly evolving field of histone acetylation as a key regulatory mechanism for gene expression. The authors describe what has been learned about these proteins, including the identification of the enzymes, the elucidation of the enzymatic mechanisms of action, and the identification of their substrates and their partners. They also review the structures that have been solved for a number of enzymes-both alone and in complex with small molecule inhibitors-and the biological roles of the several histone deacetylases (HDAC) genes that have been knocked out in mice.
Camptothecins in Cancer Therapy
A critical review our current understanding of camptothecins, their shortcomings, and of the possibilities for improving their clinical performance. The authors discuss new camptothecin analog development, drug delivery issues for optimizing their anticancer activity, and their potential use in a variety of different cancers. Additional chapters describe what is known about the biochemistry, the pharmacology, and the chemistry of the camptothecins, including the mechanism of topoisomerase and how camptothecins poison this enzyme, the use of animal models in defining the anticancer potential of camptothecins, and the question of camptothecin resistance.
EGFR Signaling Networks in Cancer Therapy
The epidermal gro wth factor (EGF ) receptor and its downstream signal transduction networks have been implicated in the ontology and maintenance of tumor tissues, which has motivated the discovery and development of molecularly targeted anti-EGF receptor therapies. Over decades of study, the EGF receptor structure, its ligand binding domains, the physical biochemistry underlying its intrinsic tyrosine kinase catalytic function and the modular interactions with SH2, PTB, and SH3 domain containing signaling adaptor p- teins required for signal transduction, have been extensively dissected. Not only is the EGF receptor the nexus of many streams of information, but it also forms one part of a c...
Biomarkers in Breast Cancer
Expert laboratory and clinical researchers from around the world review how to design and evaluate studies of tumor markers and examine their use in breast cancer patients. The authors cover both the major advances in sophisticated molecular methods and the state-of-the-art in conventional prognostic and predictive indicators. Among the topics discussed are the relevance of rigorous study design and guidelines for the validation studies of new biomarkers, gene expression profiling by tissue microarrays, adjuvant systemic therapy, and the use of estrogen, progesterone, and epidermal growth factor receptors as both prognostic and predictive indicators. Highlights include the evaluation of HER2 and EGFR family members, of p53, and of UPA/PAI-1; the detection of rare cells in blood and marrow; and the detection and analysis of soluble, circulating markers.
