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 1 alpha (HIF-1 alpha), 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-1a overexpression and poor outcome in clinical series. This month in BMC Medicine, Dales et al. report on splice variants of HIF-1a in fresh frozen tissue samples of early human breast cancer, finding an association of mRNA levels of the variant HIF-1 alpha(TAG) 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.