Since first coming on the market in 1998, the erectile dysfunction drug Viagra has improved the sex lives of countless men. Now new research has suggested that phosphodiesterase 5 (PDE5) inhibitors like Viagra could also help women – but not how you think.
Researchers in California have shown that sildenafil (Viagra) and a similar drug called vardenafil can improve the delivery of the chemotherapeutic drug Herceptin (trastuzumab) in women with breast cancer that has spread to the brain. Their studies in mice have found that PDE5 inhibitors help Herceptin cross the blood vessels of brain tumours into the heart of the cancer, thus improving the therapeutic efficacy of Herceptin for brain metastases from primary tumors.
Although only about 22,000 patients in the US are diagnosed with a primary brain tumor each year, nearly 10 times that many people develop brain tumors from cancers that began elsewhere in the body. For example, one study found that 36% of women receiving Herceptin for breast cancer developed brain metastases.
These secondary brain tumours are very hard to treat thanks to the fact that chemotherapy drugs can’t cross the walls of the tumour’s blood vessels – the blood-brain tumor barrier – and into the cancer. “Mother Nature created this barrier to protect our brains from dangerous substances, but here we need to get through the barrier to deliver the drugs, and that’s a problem,” said study author Julia Y Ljubimova, a research scientist at the Cedars-Sinai Maxine Dunitz Neurosurgical Institute in Los Angeles. This means that drugs that can kill the primary tumour in the breast or lung aren’t effective on secondary tumours in the brain.
Ljubimova and her colleagues looked at the effects of PDE5 inhibitors on drug delivery in mice whose brains had been implanted with human lung and breast tumors. Oral administration of vardenafil to such mice doubled the uptake of Herceptin by brain tumours. Importantly, vardenafil had no effect on the uptake of Herceptin in neighbouring healthy tissue, an unfortunate effect of many chemotherapy drugs that is responsible for making cancer patients feel so awful and lose their hair.
Furthermore, combination treatment of mice with vardenafil and Herceptin increased the survival time of these mice by 20% compared with those that received Herceptin only. This effect was only seen in mice whose brain tumours were positive for HER2, the growth factor targeted by Herceptin, and not those that were HER negative, indicating that the survival benefit was indeed due to an increase in the amount of Herceptin reaching the tumors.
“Now that we’ve demonstrated that big molecules can cross the blood-brain tumor barrier, we’re going to continue this strategy with other big molecule drugs, such as nanomedicine drugs” said Ljubimova. “This opens a new world for brain tumor treatments.”
Hu J et al. (2010) Phosphodiesterase Type 5 Inhibitors Increase Herceptin Transport and Treatment Efficacy in Mouse Metastatic Brain Tumor Models. PLoS ONE 5 (4). DOI: 10.1371/journal.pone.0010108