Hypoxia in cancer: significance and impact on clinical outcome.

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Cancer Metastasis Rev. 2007 Jun;26(2):225-39.
Vaupel P, Mayer A.Institute of Physiology and Pathophysiology, University of Mainz, Duesbergweg 6, 55099 Mainz, Germany.

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a characteristic feature of locally advanced solid tumors, has emerged
as a pivotal factor of the tumor (patho-)physiome since it can promote
tumor progression and resistance to therapy. Hypoxia represents a
"Janus face" in tumor biology because (a) it is associated with
restrained proliferation, differentiation, necrosis or apoptosis, and
(b) it can also lead to the development of an aggressive phenotype.
Independent of standard prognostic factors, such as tumor stage and
nodal status, hypoxia has been suggested as an adverse prognostic
factor for patient outcome. Studies of tumor hypoxia involving the
direct assessment of the oxygenation status have suggested worse
disease-free survival for patients with hypoxic cervical cancers or
soft tissue sarcomas. In head & neck cancers the studies suggest
that hypoxia is prognostic for survival and local control. Technical
limitations of the direct O(2) sensing technique have prompted the use
of surrogate markers for tumor hypoxia, such as hypoxia-related
endogenous proteins (e.g., HIF-1alpha, GLUT-1, CA IX) or exogenous
bioreductive drugs. In many - albeit not in all - studies endogenous
markers showed prognostic significance for patient outcome. The
prognostic relevance of exogenous markers, however, appears to be
limited. Noninvasive assessment of hypoxia using imaging techniques can
be achieved with PET or SPECT detection of radiolabeled tracers or with
MRI techniques (e.g., BOLD). Clinical experience with these methods
regarding patient prognosis is so far only limited. In the clinical
studies performed up until now, the lack of standardized treatment
protocols, inconsistencies of the endpoints characterizing the
oxygenation status and methodological differences (e.g., different
immunohistochemical staining procedures) may compromise the power of
the prognostic parameter used.