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Tumour Hypoxia

Molecular Mechanisms and Clinical Implications


Silvia Pastorekova and Juraj Kopacek

Insufficient supply of oxygen, i.e. hypoxia, typically occurs in a broad range of solid tumours due to aberrant vasculature. It is a key component of tumour microenvironment that affects many biological processes at molecular, cellular and tissue levels. Adaptive responses to oxygen deficiency shape signal transduction, cell metabolism, proliferation, differentiation, survival, angiogenesis, immunosurveillance etc. and thereby contribute to tumour invasion and metastasis. Presence of tumour hypoxia is significantly associated with poor prognosis and therapy resistance. Therefore, it represents a clinically relevant phenomenon that can be exploited for improvement of existing diagnostic and treatment procedures as well as for development of new targeted strategies. This book summarizes the current state of knowledge on hypoxia-regulated pathways and their biological consequences and describes promising approaches to clinical application of this knowledge. It is the first concise and complex guide to understanding principal basic and medical aspects of tumour hypoxia.
Contents: Norma Masson/Peter J. Ratcliffe: Oxygen sensing by HIF hydroxylases – Thomas M.F. Connor/Patrick H. Maxwell: VHL inactivation – Carine Michiels: Oncogenic activation of HIF pathway – Katarzyna J. Nytko/Daniel P. Stiehl/Roland H. Wenger: PHD oxygen sensor function and antioxidants – Agnieszka Loboda/Halina Was/Urszula Florczyk/Alicja Jozkowicz/Jozef Dulak: Hypoxia-driven angiogenesis and other modes of blood vessel formation in tumours – Erik Olai Pettersen: Cell cycle alterations by hypoxic microenvironment – Eoin P. Cummins/Susan F. Fitzpatrick/Cormac T. Taylor: The role of NF-κB in hypoxia-induced gene expression – Roman Hrstka/Petr Müller/Philip J. Coates/Borivoj Vojtesek: Hypoxia and p53 – Thomas Kietzmann: Hypoxia: a powerful signal to induce metabolic changes – Eliska Svastova/Silvia Pastorekova: Hypoxia, regulation of pH and cell migration/invasion – Agnes Görlach: Reactive oxygen species and hypoxia signaling – Olga Krizanova: Calcium transport in hypoxia – Sandra Winning/Joachim Fandrey: HIF and inflammation – Martina Takacova/Tereza Goliasova/Juraj Kopacek: Hypoxia and oncogenic viruses – Sarah Peeters/Philippe Lambin/Ludwig Dubois: Noninvasive hypoxia imaging – Bart Reymen/Philippe Lambin: Hypoxia, hypoxia response and conventional anti-cancer therapy – Kaye J. Williams/Stephanie R. McKeown: Targeting hypoxic cells with bioreductive prodrugs – Annamaria Rapisarda/Nicole Fer/Giovanni Melillo: Targeting the hypoxic tumour microenvironment: a unique role for HIF-1 inhibitors – Claudiu T. Supuran: New drugs interfering with pH regulation in hypoxic tumours.