Tumor hypoxia and gene expression - Implications for malignant progressionand therapy

Most histopathological classifications of human cancers include significant numbers of hypoxic cells. There is increasing evidence that, at least in c ertain types of human solid tumors, there is a positive relationship betwee n the presence of hypoxia and poor outcome after radiation therapy alone or radiation combined with other therapies. Hypoxia appears to be an independ ent prognostic factor. There is evidence for enhanced malignant progression associated with hypoxia, including locoregional invasion and distant metas tases. The presence of hypoxia may negatively affect outcome by induction o f radiation resistance by the classical oxygen effect and/or by effects on gene expression and malignant progression, causing more aggressive locoregi onal and distant disease. It is now clear that hypoxia has the potential to influence expression of genes and activities of associated proteins that r egulate growth and tissue homeostasis, resulting in cellular phenotypic het erogeneity. The molecular pathways involved in signaling and regulating cha nges in gene activities in response to external stresses such as hypoxia ar e becoming known. Identification of patients with hypoxic tumors will lead to improved selective therapy.