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Scientists home in on reasons behind cancer drug trial disappointment

Scientists have discovered a ‘hidden’ mechanism which could explain why some cancer therapies which aim to starve the tumour of its blood supply are failing cancer trials.

Numerous angiopoietin-blocking therapies are currently in clinical trials for ovarian cancer and other cancers. But despite promising earlier results, some of these therapies are not improving patient survival as much as was expected.*

Many current angiopoietin-blocking therapies work by inhibiting a specific cell pathway which promotes blood vessel growth. The pathway involves angiopoietin-1 and angiopoietin-2 proteins and also another protein, called Tie-2.

However this latest research, supported by Worldwide Cancer Research and published in Nature Communications January 30th, 2015**, suggests the existence of an alternative angiopoietin-mediated mechanism which ‘bypasses’ Tie-2.

Lead researcher, Dr Pipsa Saharinen, at the University of Helsinki*** said: “What we have found in our studies on cells and in mice, is another angiopoietin-2 cell pathway which could promote blood vessel growth. This pathway is not necessarily targeted by current angiopoietin-blocking therapies, and this could help explain why some of the trials have not produced as much benefit as we might have hoped.”

“We still need to confirm what we’re seeing in normal cells is happening in tumors as well” says Dr Saharinen. “And we have to figure out what actually happens inside the body. Then we can work out for sure how blocking this new angiopoietin pathway affects tumour blood vessels. Ultimately, I think these results could help explain some of the confusing trial results we’ve seen.”

Dr Helen Rippon, Head of Research at Worldwide Cancer Research said: “Around 19 women in the UK are diagnosed with ovarian cancer every day, and better treatments are desperately needed. There is still a lot of work to do to, but this finding could ultimately help us develop more effective anticancer treatments which work by blocking a tumour’s blood supply.”


* See Phase III setback for lead angiopoietin inhibitor. DOI:10.1038/nrd4509, Published online 01 December 2014

** Hakanpaa et al, 2015. Endothelial destabilization by angiopoietin-2 via integrin ?1 activation. DOI: 10.1038/ncomms6962, published 30 January 2015.

*** Research carried out at Wihuri Research Institute (Angiopoietin growth factors and their possible therapeutic use in the vasculature), University of Helsinki, University of Turku, and University of Oulu.

Source: Worldwide Cancer Research