Potential for novel vascular targeting agent for cancer
Clinical evidence has emerged that nitric oxide has a role in maintaining
tumour blood supply and that inhibition of its synthesis results in a
sustained reduction in tumour blood volume. The research is published
online in The
Lancet Oncology on
15 January 2006.
Animal studies have suggested that nitric oxide synthase may have a role
in maintaining tumour blood supply. Nitric oxide increases tumour vascularisation
through angiogenesis, which is related to increased tumour growth, and
is the final mediator of angiogenesis stimulated by vascular endothelial
growth factor, the major factor implicated in angiogenesis of many human
tumours.
Researchers gave a single dose of the nitric oxide synthase inhibitor
N-nitro-L-arginine (L-NNA) to 18 volunteers who had non-small cell lung
cancer, prostate cancer or cervical cancer. They found that, in the eight
patients who underwent CT scanning, tumour blood flow decreased one hour
after treatment (mean decrease of 42.9 per cent, range 12.0–62.1,
P=0.007). This decrease was sustained for up to 24 hours and was associated
with an increase in the number of non-perfused tumour pixels, indicating
a decrease in functional vascularity. Toxic effects were cardiovascular
and self-limiting, including a drop in pulse rate and an increase in
blood pressure.
“The sustained reductions in tumour blood volume after a single
dose of L-NNA seem promising for use as a novel vascular targeting agent,” say
the researchers. However, the biological role of nitric oxide in cancer
remains unclear, they add. Further studies will be needed to relate these
vascular findings to clinical outcome, they conclude. |
The
Pharmaceutical Journal
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