Tumour Hypoxia – Molecular Mechanisms and Clinical Relevance

Česká verze

Authors: M. Takáčová ^1,2 ; S. Pastoreková ^1,2
Authors place of work: Regionální centrum aplikované molekulární onkologie, Masarykův onkologický ústav, Brno ¹; Oddelenie molekulárnej medicíny, Virologický ústav, Slovenská akadémia vied, Bratislava, Slovenská republika ²
Published in the journal: Klin Onkol 2015; 28(3): 183-190
Category: Přehledy
doi: https://doi.org/10.14735/amko2015183

Summary

Oxygen is absolutely essential for correct functioning of living organisms and alterations in its concentration lead to serious consequences. In tumor tissues, oxygen plays an important role in energy production and modulation of red- ox balance. Insufficient oxygen supply within tissues results in hypoxia that is a characteristic feature of the tumor microenvironment. Hypoxia- inducible transcriptional factor represents a key executor of a cellular and molecular response to hypoxia and can activate the expression of more than hundred genes involved in various essential cellular processes. From the clinical point of view, phenotypic alterations caused by hypoxia are serious. Tumor hypoxia has been associated with resistance to therapy, disease progression and recurrence as well as increased mortality. Therefore, intratumoral hypoxia represents a clinically relevant problem, and its detection within tumors is very important for patient stratification for a suitable treatment. Currently available strategies directed towards the detection of hypoxic regions within tumor tissue suffer from numerous limitations e. g. invasiveness, inaccessibility of tumor tissue, low sensibility, inaccurate interpretation etc. On the other hand, the use of an intrinsic endogenous hypoxic marker, which can be detected through immunohistochemistry, is relatively simple, routinely available, and reproducible and can be performed on both prospective and retrospective samples. These include carbonic anhydrase IX (CA IX), one of the most strongly hypoxia-induced proteins and a prominent indicator of chronic hypoxia. Moreover, hypoxia-induced proteins (including CA IX) are also potential targets of anticancer therapy, and their practical application is a subject of intense research.

Key words:
hypoxia – tumor microenvironment – hypoxia- inducible factor – resistance – carbonic anhydrase IX

This study was supported by European Regional Development Fund and the state budget of the Czech Republic for Regional Centre for Applied Molecular Oncology – RECAMO (CZ.1.05/2.1.00/03.0101), the project MEYS – NPS I – LO1413, European Regional Development Fund and the State Budget of the Slovak Republic (ITMS 26240220087) and the Slovak Scientific Grant Agency VEGA 2/0152/12.

The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study.

The Editorial Board declares that the manuscript met the ICMJE “uniform requirements” for biomedical papers.

Submitted:
27. 3. 2015

Accepted:
13. 4. 2015

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