Blood pressure drug improves effect of chemotherapy in mice
A tried and tested blood pressure drug may improve the effects of chemotherapy, US scientists have shown.
Researchers from Massachusetts General Hospital (MGH) have uncovered how the blood pressure drug losartan opens up blood vessels in tumours in mice and allows more chemotherapy to reach the cancer.
Losartan belongs to a class of drugs called angiotensin inhibitors, which have been used as safe blood pressure medications for over a decade.
Dr Rakesh K Jain, director of the Steele Laboratory for Tumor Biology at MGH, said: "Unlike anti-angiogenesis drugs, which improve tumour blood flow by repairing the abnormal structure of tumour blood vessels, angiotensin inhibitors open up those vessels by releasing physical forces that are applied to tumour blood vessels when the gel-like matrix surrounding them expands with tumour growth."
The team began to look at the physical reasons why chemotherapy drugs might not reach their intended target.
Collagen is a major part of the matrix that surrounds tumour blood vessels and previous studies show that losartan inhibits the formation of collagen.
The latest study, published in Nature Communications, looked at whether losartan and other drugs can affect the forces within tumours that compress and collapse blood vessels. The stresses occur when specialised cells in the tumours known as cancer-associated fibroblasts (CAFs) multiply and produce collagen and another component of the matrix called hyaluronan.
Working with mouse models, the team found that losartan suppressed the activity of CAFs. This inhibited the production of collagen and hyaluronan and prevented compression of blood vessels within tumours.
The study found that combined treatment with losartan and standard chemotherapy delayed tumour growth and extended survival in mouse models of breast and pancreatic cancer.
Dr Jain said: "Increasing tumour blood flow in the absence of anti-cancer drugs might actually accelerate tumour growth, but we believe that combining increased blood flow with chemotherapy, radiation therapy or immunotherapy will have beneficial results."
"Based on these findings in animal models, our colleagues at the MGH Cancer Center have initiated a clinical trial to test whether losartan can improve treatment outcomes in pancreatic cancer."
Dr Holger Gerhardt, a Cancer Research UK expert on blood vessel growth, said: “It’s not always enough to have an effective chemotherapy, as tumours can develop barriers that stop the drug reaching its target.”
“This important research helps explain why blood pressure drugs like losartan could help chemotherapy reach tumours, by stopping cells in the tumour matrix from producing certain molecules. This in turn reduces the tumour pressure and allows blood vessels to re-open and deliver the chemotherapy.”
He also said that a potential "exciting by-product" of this CAF suppression could be that it cuts the chance of cancer spreading, as work by researchers such as Cancer Research UK’s Dr Erik Sahai shows that cancer cells follow CAFs through the matrix as they start to spread.
Dr Emma Smith, Cancer Research UK's senior science communications officer, said that the fact that these drugs are already widely used to treat high blood pressure could cut down the amount of time it takes to test their potential in treating cancer.
But she cautioned that they may not be safe for all patients or when combined with other cancer treatments, and clinical trials would help answer these questions.
Copyright Press Association 2013
- Chauhan V.P. et al. (2013). Angiotensin inhibition enhances drug delivery and potentiates chemotherapy by decompressing tumour blood vessels. Nature Communications, 4 DOI: 10.1038/ncomms3516