The imbalance between rapidly proliferating tumor cells and inadequate and inefficient tumor vasculature leads to a decrease in oxygen levels (hypoxia and/or anoxia) in tumor tissues. Intra-tumor hypoxia profoundly affects the biological behavior of cancer cells, which become resistant to conventional therapies and acquire a more invasive and metastatic phenotype. Hypoxia is a hallmark of the malignant phenotype and a key feature of the tumor microenvironment. Hypoxia Inducible Factor 1 (HIF-1) is a master regulator of the transcriptional response to oxygen deprivation. HIF triggers the expression of genes whose products induce angiogenesis, decrease oxygen consumption, switch metabolism to glycolysis, maintain a stem cell phenotype and select for more invasive and metastatic cells. Therapeutic approaches targeting HIF, directly or downstream mediators of its transcriptional activity, are being developed. Intra-tumor hypoxia is a topic has been gaining scientific interest over the last few years for its wide involvement in many physiological and pathological processes.
This volume will cover the latest research and translational aspects associated with intra-tumor hypoxia, along with opportunities for drug development offered by this unique feature of the tumor microenvironment. The ongoing efforts to translate our understanding of the biology underlying intra-tumor hypoxia in viable therapeutic options face many challenges, but this book will provide an opportunity for an in-depth analysis of the fundamental mechanisms implicated in the adaption to low oxygen levels and will scrutinize the potential for opportunities that are being pursued in both research and the drug development industry.
Features comprehensive and systematic analysis of biological and therapeutic targets associated with intra-tumor hypoxia
Focuses on translational aspects associated with intra-tumor hypoxia
Explores the opportunities for drug development offered by this unique feature of the tumor microenvironments
The tremendous progress in our understanding of the molecular mechanisms underlying tumor hypoxias has generated a great deal of enthusiasm and provides new opportunities to better understand and target the tumor microenvironment. This book emphasizes how changes in oxygen levels in the tumor microenvironment impact cancer cell biology and provide new opportunities for cancer therapy and the contribution of world renowned experts in tumor hypoxia makes this text an invaluable tool for understanding how hypoxia impacts the biology, imaging and therapy of human cancers. Basic and translational scientists alike will find this book to be a source of updated information and an opportunity to further strategic thinking in order to better understand and target the complexity of the hypoxic tumor microenvironment. This book is a reference tool for students, scientists and clinicians who are interested in the role of hypoxia in cancer biology and therapy.
Preface.- Hypoxia and breast cancer metastasis.- Hypoxia and the DNA damage response.- Hypoxia and non-coding RNAs.- Hypoxia and ROS.- Hypoxia and gene expression.- Carbonic anhydrase IX: from biology to therapy.- Imaging the hypoxic tumor microenvironment in preclinical models.- Clinical imaging of hypoxia.- Hypoxia, antiangiogenic therapy and metastasis.- UPR and therapeutic opportunities.- Targeting the hypoxic phenotype.- Marianne Nordsmark: Hypoxia and Radiation therapy.- Pharmacological strategies targeting hypoxia.- Targeting the hypoxic tumor microenvironment.- Clinical exploitation of hypoxia.- Index.