Oxygen status of malignant tumors: pathogenesis of hypoxia and significance for tumor therapy.

Abstract:

:Hypoxic areas are a characteristic property of solid tumors. Hypoxia results from an imbalance between the supply and consumption of oxygen. Major pathogenetic mechanisms for the emergence of hypoxia are (1) structural and functional abnormalities in the tumor microvasculature; (2) an increase in diffusion distances; and (3) tumor- or therapy-associated anemia leading to a reduced O2 transport capacity of the blood. There is pronounced intertumor variability in the extent of hypoxia, which is independent of clinical size, stage, histopathologic type, and grade. Local recurrences have a higher hypoxic fraction than primary tumors. Tumor hypoxia is intensified in anemic patients, especially in tumors with low perfusion rates. Tumor hypoxia is a therapeutic problem, as it makes solid tumors resistant to sparsely ionizing radiation and some forms of chemotherapy. Hypoxia also may modulate the proliferation and cell cycle position of tumor cells and, in turn, the amount of cells destroyed following therapy. Recent clinical studies suggest that hypoxia can enhance malignant progression and increase aggressiveness through clonal selection and genome changes. As a result, loss of differentiation and apoptosis, chaotic angiogenesis, increased locoregional spread, and enhanced metastasis can further increase resistance to therapy and affect long-term prognosis. Hypoxia is a powerful, independent prognostic factor in cervix cancers, carcinomas of the head and neck, and in soft-tissue sarcomas.

journal_name

Semin Oncol

journal_title

Seminars in oncology

authors

Vaupel P,Kelleher DK,Höckel M

doi

10.1016/s0093-7754(01)90210-6

subject

Has Abstract

pub_date

2001-04-01 00:00:00

pages

29-35

issue

2 Suppl 8

eissn

0093-7754

issn

1532-8708

pii

asonc0280029e

journal_volume

28

pub_type

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