%0 Journal Article
%T Hypoxia-specific targets in cancer therapy: role of splice variants
%A Dirk Vordermark
%J BMC Medicine
%D 2010
%I BioMed Central
%R 10.1186/1741-7015-8-45
%X See research article: http://www.biomedcentral.com/1741-7015/8/44 webciteThis month in BMC Medicine, Dales and coworkers report on the expression of hypoxia-inducible factor 1¦Á (HIF-1¦Á) splice variants in human breast cancer [1]. This work represents an early and preliminary investigation that may become part of a process leading to further individualisation of cancer therapy, specifically addressing the role of hypoxic tumour cells.Low oxygenation of tumour cells is a well known adverse prognostic factor in cancer treatment. It occurs due to (a) rapid tumour growth with resulting long diffusion distances from the nearest blood vessel ('diffusion-limited hypoxia'), as well as (b) the chaotic structure of pathological tumour vessels and resulting inadequate perfusion in part of these vessels ('perfusion-limited hypoxia') [2]. It was established mainly in the 1990 s that a low pretreatment intratumoural partial oxygen pressure (pO2), as determined by needle electrode measurement, is associated with a poor outcome of treatment, in particular radiotherapy but also surgical treatment, of cervical cancer or head and neck cancer [3,4]. This association has been explained by the reduced ability of ionizing radiation to produce DNA damage in the absence of oxygen as well as, more recently, by an increased potential of hypoxic tumour cells for proliferation, invasion, metastasis and angiogenesis [2].For decades, investigators have attempted to overcome the treatment resistance of hypoxic tumours in clinical trials, for example by adding so-called 'hypoxic radiosensitiser' drugs to the regimens or introducing hyperbaric oxygen. Although many of the individual trials were negative, a modern meta-analysis confirms the efficacy of hypoxia-directed treatments [5]. While previous strategies were directed at all patients with a given tumour diagnosis, more modern approaches combine (a) the selection of patients with particularly hypoxic tumours and (b) the addition of hypoxia-specif
%U http://www.biomedcentral.com/1741-7015/8/45