Tumour Hypoxia: Impact on Biology, Prognosis and Treatment of Solid Malignant Tumours

Klinik für Radioonkologie, Universität Tübingen, Germany.
Onkologie (Impact Factor: 0.86). 03/2004; 27(1):83-90. DOI: 10.1159/000075611
Source: PubMed


Tumour hypoxia is a major constraint for radiotherapy and many types of chemotherapy. A variety of different pathogenetic mechanisms contribute to the development of hypoxia in solid tumours. Hypoxia is associated with unfavourable prognosis, regardless of the treatment modality applied. Two different effects have been considered to explain the deleterious effects of hypoxia on the outcome of tumour patients. The first aspect encompasses the direct interference of hypoxia with antineoplastic treatment modalities. The efficacy of ionizing radiation, but also of a variety of cytotoxic drugs and cytokines rely directly on adequate oxygen tensions. The second aspect concerns the effects of hypoxia on the biology of tumour and stromal cells. Hypoxia is related to malignant progression, increased invasion, angiogenesis and an increased risk of metastasis formation. Possibly, hypoxia is furthermore a stressor which selects cells with increased resistance to apoptosis and thereby indirectly contributes to treatment resistance. This article reviews in brief the specific pathophysiology of tumour oxygenation and its implications for prognosis, tumour treatment and biology.

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    • "In addition, some solid tumours are found to have necrotic (dead) cores, a direct effect of long-standing tissue hypoxia [8] [9]. Tumour hypoxia has been demonstrated to reduce the efficacy of many standard cytotoxic drugs used in the treatment of cancer [10]. This is due to ineffective penetration of the drug into the hypoxic mass of the tumour, due to poor vascularisation . "
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    ABSTRACT: Despite substantial investment in prevention, treatment and aftercare, cancer remains a leading cause of death worldwide. More effective and accessible therapies are required. A potential solution is the use of endospore forming Clostridium species, either on their own, or as a tumour delivery vehicle for anti-cancer drugs. This is because intravenously injected spores of these obligate anaerobes can exclusively germinate in the hypoxic/necrotic regions present in solid tumours and nowhere else in the body. Research aimed at exploiting this unique phenomenon in anti-tumour strategies has been ongoing since the early part of the 20th century. Only in the last decade, however, has there been significant progress in the development and refinement of strategies based on spore-mediated tumour colonisation using a range of clostridial species. Much of this progress has been due to advances in genomics and our ability to modify strains using more sophisticated gene tools.
    Research in Microbiology 01/2015; 166(4). DOI:10.1016/j.resmic.2014.12.006 · 2.71 Impact Factor
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    • "With few exceptions, solid tumors have regions with little or no oxygen [1] [2] [3]. This is due to poor vascularization and is called hypoxia (low oxygen tension) or anoxia (no oxygen). "
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    ABSTRACT: The sections in this article areIntroductionThe Role of Oxygen in Photodynamic Therapy: 1O2 GenerationDependence of the Photosensitizing Effect on O2 ConcentrationThe Oxygenation Status in Tumors and Normal TissuesPDT-Induced Reduction of Tumor OxygenationO2 Consumption (Primary Reduction)Vascular Damage (Secondary Reactions)Photosensitizer Photobleaching (Secondary Reactions)Methods to Reduce Tumor Deoxygenation During PDTLow Fluence RatesFractionated Light ExposureOther Methods Changes of Quantum Yields Related to Photosensitizer RelocalizationChanges of Optical Penetration Caused by Changes in O2 ConcentrationConclusion Keywords:photodynamic therapy;oxygen;photosensitization;oxygenation;tumor deoxygenation;cancer
    Handbook of Biophotonics, 01/2013; , ISBN: 9783527643981
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    • "A unique feature of solid cancers is that their rapid growth often results in reduced oxygen availability due to the formation of inadequate or aberrant vasculature [5]. The hypoxic fraction of solid tumors is resistant to radiotherapy [6] and conventional chemotherapy [7]–[10], and hypoxia correlates with poor therapeutic outcome [7], [8], [11], [12]. At the molecular level, the transcription factor Hypoxia Inducible Factor-1 (HIF-1) has been identified as the key orchestrator of the biological response to hypoxia due to its transactivation of genes that are involved in many aspects of malignant tumor growth from cell survival and metabolism to angiogenesis and invasion [13]–[16]. "
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