Hypoxia in breast cancer: role of blood flow, oxygen diffusion distances, and anemia in the development of oxygen depletion.

Abstract:

:Heterogeneously distributed hypoxic areas are a characteristic property of locally advanced breast cancers. Hypoxia results from an imbalance between the supply and consumption of oxygen (O2). Major pathogenetic mechanisms for the emergence of hypoxia are (i) structural and functional abnormalities in the tumor microvasculature, (ii) an adverse diffusion geometry, and (iii) tumor-related and therapy-induced 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, histology and grade. Hypoxia is intensified in anemic patients, especially in tumor (areas) with low perfusion rates. Tumor hypoxia is a therapeutic problem since it makes solid tumors resistant to sparsely ionizing radiation, some forms of chemotherapy, and photodynamic therapy. However, besides more direct mechanisms involved in the development of therapeutic resistance, there are, in addition, indirect machineries that can cause barriers to therapies. These include hypoxia-mediated alterations in gene expression, proteomic and genomic changes, and clonal selection. These in turn can drive subsequent events that are known to further increase resistance to therapy in addition to critically affecting long-term prognosis.

journal_name

Adv Exp Med Biol

authors

Vaupel P,Mayer A,Briest S,Höckel M

doi

10.1007/0-387-26206-7_44

subject

Has Abstract

pub_date

2005-01-01 00:00:00

pages

333-42

eissn

0065-2598

issn

2214-8019

journal_volume

566

pub_type

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