Tumour hypoxia: impact on biology, prognosis and treatment of solid malignant tumours.
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.
Weinmann
M
M
Klinik für Radioonkologie, Universität Tübingen, Germany. martin.weinmann@med.uni-tuebingen.de
Belka
C
C
Plasswilm
L
L
D017209:Apoptosis / Q000187:drug effects / Q000235:genetics / Q000502:physiology* / Q000528:radiation effects; D014408:Biomarkers, Tumor / Q000235:genetics; D015687:Cell Hypoxia / Q000235:genetics / Q000502:physiology*; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics / Q000502:physiology* / Q000528:radiation effects; D003131:Combined Modality Therapy; D004268:DNA-Binding Proteins / Q000235:genetics; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009361:Neoplasm Invasiveness / Q000235:genetics; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000503:physiopathology* / Q000532:radiotherapy; D009687:Nuclear Proteins / Q000235:genetics; D011379:Prognosis; D014157:Transcription Factors; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; C497442:HIF1A protein, human; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009687:Nuclear Proteins; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53