Article

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

ABSTRACT

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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    • "Several reports have described a close relationship between genetic stability of the tumor and the selective pressure of the tumor microenvironment [6]. Many biomarkers predicting the response to chemotherapy are suggested to be linked to pathways of cell survival that are activated as adaptive response mechanisms in stressing microenvironments such as poor nutrient supply or low oxygen levels [7]. One candidate that is suggested to play an important role in cancer cell survival is class III β-tubulin (TUBB3) "
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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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    • "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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