Hypoxia-specific targets in cancer therapy: role of splice variants

Dirk Vordermark

doi:10.1186/1741-7015-8-45

Abstract

Tumour hypoxia is a well known adverse prognostic factor in the treatment of solid tumours. Hypoxia-inducible factor 1α (HIF-1α), 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-1α overexpression and poor outcome in clinical series. This month in BMC Medicine, Dales et al. report on splice variants of HIF-1α in fresh frozen tissue samples of early human breast cancer, finding an association of mRNA levels of the variant HIF-1αTAG 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.See research article: http://www.biomedcentral.com/1741-7015/8/44

Highlights

This month in BMC Medicine, Dales and coworkers report on the expression of hypoxia-inducible factor 1α (HIF-1α) splice variants in human breast cancer [1]
While previous strategies were directed at all patients with a given tumour diagnosis, more modern approaches combine (a) the selection of patients with hypoxic tumours and (b) the addition of hypoxia-specific treatment modalities to standard radiotherapy/chemotherapy only in these subgroups
Such observations were made in breast cancer [11,12], the topic studied by Dales et al Despite its negative prognostic relevance, tumour hypoxia has been discussed as an opportunity for tumour-specific treatment approaches, for low pO2 levels as found in solid tumours very rarely occur in normal tissues [13]

Summary

Background

This month in BMC Medicine, Dales and coworkers report on the expression of hypoxia-inducible factor 1α (HIF-1α) 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, addressing the role of hypoxic tumour cells

Discussion

Conclusions

Overgaard J

Semenza GL

13. Brown JM

15. Dewhirst MW