The Tumor Microenvironment

Description

The field of cancer biology and developmental therapeutics is continually evolving as new methodologies are developed and new targets are discovered. Although multiple therapeutics directly target the malignant cells these drugs rarely prevent recurrence of disease or the progression of metastasis. The complex biology of tumors presents challenges in designing treatments that will eliminate the malignant cells as well as the supporting network of vasculature and stroma that allows for the comparison of tumors to developing organs in embryos. In addition to blood vessels and malignant cells, tumors consist of fibroblasts, immune and inflammatory cells, and a myriad of proteins that comprise the extracellular matrix. Effective eradication of malignant disease requires therapeutic strategies that factor in targeting the tumor microenvironment. In the past decade, a new class of anticancer drugs has emerged that interferes with tumor angiogenesis; however the clinical benefit from treatment with the first generation antiangiogenic agents added to the standard of care is often modest. Thus, there remains a critical need to understand the tumor microenvironment and to develop anti-cancer therapies that address this aspect of malignant disease. The first edition of The Tumor Microenvironment is intended to give a current perspective on the role of the tumor microenvironment in malignant progression and detail strategies for novel therapies directed towards the cellular matrix. This book explores the many biological and physiological aspects of the tumor as a tissue and includes chapters on the variety of cells that influence tumor growth and spread as well as the cell-associated and soluble proteins that can promote invasion and metastasis. Several chapters describe endothelial cells and pericytes that form tumor vasculature. Insights into the role of progenitor and stem cells are included. The contribution of the supporting stroma is addressed in addition to cell-cell signaling and cell-matrix interactions. Additional chapters describe the influence of infiltrating cells of the immune system on tumor growth. The Tumor Microenvironment is the definitive text detailing cutting edge research by experts in the field and will be a valued resource in the study of this important area of cancer biology for many years to come. Front Matter....Pages i-xviii Front Matter....Pages 1-1 Combination Strategies Targeting Hypoxia Inducible Factor 1 (HIF-1) for Cancer Therapy....Pages 3-21 The Tumor Microenvironment: New Insights into Regulation of Tumor pH by Carbonic Anhydrases....Pages 23-41 Hypoxia, Gene Expression, and Metastasis....Pages 43-58 Molecular Mechanisms Regulating Expression and Function of Cancer-Associated Carbonic Anhydrase IX....Pages 59-90 Glycolytic Pathway as a Target for Tumor Inhibition....Pages 91-118 Front Matter....Pages 119-119 Aberrant DNA Methylation in Cancer Cells....Pages 121-132 DNA Repair and Redox Signaling....Pages 133-168 Cancer Stem Cells and Microenvironment....Pages 169-185 Epithelial–Mesenchymal Transition in Development and Diseases....Pages 187-211 Invasion and Metastasis....Pages 213-228 Dormancy of Disseminated Tumor Cells: Reciprocal Crosstalk with the Microenvironment....Pages 229-254 Front Matter....Pages 255-255 Impact of Endothelial Progenitor Cells on Tumor Angiogenesis and Outcome of Antiangiogenic Therapy: New Perspectives on an Ongoing Controversy....Pages 257-273 Bone Marrow Derived Mesenchymal Stem/Stromal Cells and Tumor Growth....Pages 275-288 Integrin Signaling in Lymphangiogenesis....Pages 289-309 Role of Pericytes in Resistance to Antiangiogenic Therapy....Pages 311-323 Tumour-Promoting Stromal Myofibroblasts in Human Carcinomas....Pages 325-349 Front Matter....Pages 351-351 Mast Cells and Tumor Microenvironment....Pages 353-370 Macrophages in the Tumor Microenvironment....Pages 371-383 The Prognostic Significance of Tumor-Infiltrating Lymphocytes....Pages 385-407 The Pro-inflammatory Milieu and Its Role in Malignant Epithelial Initiation....Pages 409-430 Front Matter....Pages 351-351 Natural Killer Cells for Adoptive Immunotherapy....Pages 431-454 Front Matter....Pages 455-455 Fibronectin....Pages 457-476 Collagen in Cancer....Pages 477-507 Integrins and Cancer....Pages 509-529 Matrix Metalloproteinases and Cancer Cell Invasion/Metastasis....Pages 531-554 Tetraspanins and Cancer Metastasis....Pages 555-598 Front Matter....Pages 599-599 Chemokines and Metastasis....Pages 601-631 Transforming Growth Factor-β in Lung Cancer, Carcinogenesis, and Metastasis....Pages 633-671 Cooperative Interactions Between Integrins and Growth Factor Signaling in Pathological Angiogenesis....Pages 673-693 The Extracellular Matrix and the Growth and Survival of Tumors....Pages 695-710 Secreted Growth Factors as Therapeutic Targets....Pages 711-732 Adrenomedullin....Pages 733-748 Back Matter....Pages 749-767