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International symposium on atherosclerosis

New cancer drugs might also find use in heart disease

The reports on this and the next page are from the XIIth International Symposium on Atherosclerosis which was held in Stockholm on June 25-29

Reports include: Bayer tests cerivastatin in renal disease ; HDL-mimetics ; Gene therapy trial in peripheral vascular disease ; Beta-blocker benefit in atherosclerosis? ; Inhibiting cholesterol absorption ; Benefit shown for treating lipid disorders in patients with diabetes

Angiogenesis inhibitors, a new class of drugs being tested in cancer treatment, might also have potential use in heart disease, the conference was told.
These drugs are in late stage trials in cancer. The idea is that they will block formation of the new blood vessels that tumours need in order to grow. However, researchers interested in the development of the drugs have had some concerns about their safety in patients who also have heart disease, the worry being that the drugs might shut off the collateral circulation that some patients with atherosclerosis depend on when their coronary vessels are blocked.

Dr Judah Folkman (Harvard medical school) told the conference that new work had provided some reassurance on this point. The collateral vessels were larger than the tumour cell capillaries that the drugs were intended to block and it appeared that the collateral circulation was not susceptible to angiogenesis inhibitors.

What was of particular interest, he said, was the finding that atheromatous plaque itself contained small capillaries and, like tumours, appeared to need these vessels to grow. His colleague Dr Karen Moulton, from Harvard, had recently found that angiogenesis inhibitors inhibited plaque growth by up to 80 per cent in mice.

So it seemed that while angiogenesis inhibitors had no detrimental effect on the collateral vessels they were able to block the new, smaller vessels. “The implication is that if a patient is receiving an angiogenesis inhibitor for cancer, and also has heart disease, we do not have to worry that it will make the heart disease worse and we can speculate that it could make it better,” Dr Folkman said. He emphasised that no clinical work investigating the drugs’ effect on atherosclerosis had been done. “It is early days, but in 10 years time we might say these drugs are of use in heart disease,” he said.

Dr Folkman pointed out that anti-angiogenesis drugs were also being investigated in eye diseases associated with excess blood vessel formation. Phase 3 trials were under way in both diabetic retinopathy and macular degeneration.

Angiogenesis inhibitors block specific growth factors involved in blood vessel formation. These include vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF). Thalidomide and interferon are among the drugs being tested as angiogenesis inhibitors. Dr Folkman said that celecoxib, a COX-2 inhibitor, had also been found recently to be a potent inhibitor of angiogenesis in animal studies. It was now being tested in cancer trials.

As well as cancer and eye diseases, excessive blood vessel formation also occurred in psoriasis, Dr Folkman said. However, clinical studies were not being carried out in this condition yet because there was a shortage of drug and alternative treatments were available.

Citation: The Pharmaceutical Journal URI: 20002120

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