Hypoxia-specific targets in cancer therapy: role of splice variants.
Tumour hypoxia is a well known adverse prognostic factor in the treatment of solid tumours. Hypoxia-inducible factor 1alpha (HIF-1alpha), a transcription factor subunit regulating a large number of hypoxia-responsive genes, is considered an attractive target for novel treatment approaches, due to a frequently reported association between HIF-1alpha overexpression and poor outcome in clinical series. This month in BMC Medicine, Dales et al. report on splice variants of HIF-1alpha in fresh frozen tissue samples of early human breast cancer, finding an association of mRNA levels of the variant HIF-1alphaTAG with adverse clinical factors (lymph node status, hormone receptor status) and poor metastasis-free survival. This preliminary study addresses the possibility that specific targeting of individual isoforms resulting from alternative splicing may play a role in HIF-1-directed treatment approaches.
Vordermark
Dirk
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Department of Radiation Oncology, Martin Luther University Halle-Wittenberg, Germany. dirk.vordermark@medizin.uni-halle.de
D000970:Antineoplastic Agents / Q000494:pharmacology; D001943:Breast Neoplasms / Q000473:pathology*; D018450:Disease Progression; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D000860:Hypoxia; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000096:biosynthesis*
D000970:Antineoplastic Agents; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit