Antiangiogenic, bioreductive and gene therapy approaches to the treatment of hypoxic tumours.

Abstract:

:Quinone based bioreductive drugs have, potentially, a very versatile use in cancer chemotherapy. They can be activated by DT-diaphorase and hence can be used to target tumour types rich in this (O2)-independent reductase enzyme. Small molecular modifications can substantially reduce specificity for DT-diaphorase and under these circumstances the quinones become much less toxic in air but retain their potent cytotoxic effects under hypoxic conditions. Our understanding of the reductive (bio) chemistry of indolequinones, in particular, has subsequently allowed us to develop a platform technology where almost any therapeutic entity can potentially be delivered, selectively, to hypoxic tumours. Antiangiogenic approaches are currently receiving a substantial amount of attention and this review brings their development into context in view of the hypoxia dependence for neovascularization. Lastly, the use of bioreductive drugs when combined with hypoxia-mediated gene therapy is described. Such an approach provides a unique dual level of specificity for targeting hypoxic tumours and potentially can provide substantial therapeutic benefit.

journal_name

Curr Pharm Des

authors

McNally VA,Patterson AV,Williams KJ,Cowen RL,Stratford IJ,Jaffar M

doi

10.2174/1381612023394548

subject

Has Abstract

pub_date

2002-01-01 00:00:00

pages

1319-33

issue

15

eissn

1381-6128

issn

1873-4286

journal_volume

8

pub_type

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