Blood-Pressure Drug May Help Improve Cancer Treatment
Losartan opens tumor blood vessels, increases drug delivery (October 1)
According to an online report in Nature Communications, the use of existing, well-established hypertension drugs could improve the outcome of cancer chemotherapy by opening up collapsed blood vessels in solid tumors.
Investigators at Massachusetts General Hospital describe how the angiotensin inhibitor losartan improved the delivery of chemotherapy drugs and oxygen throughout tumors by increasing blood flow in mouse models of breast and pancreatic cancer. A clinical trial based on the findings of this study is now under way.
“Angiotensin inhibitors are safe blood pressure medications that have been used for over a decade in patients and could be repurposed for cancer treatment,” explains senior author Rakesh K. Jain, PhD. “Unlike anti-angiogenesis drugs, which improve tumor blood flow by repairing the abnormal structure of tumor blood vessels, angiotensin inhibitors open up those vessels by releasing physical forces that are applied to tumor blood vessels when the gel-like matrix surrounding them expands with tumor growth.”
The new study looked at whether losartan and other drugs that block the action of the hormone angiotensin could release the elevated forces within tumors that compress and collapse internal blood vessels. These stresses are exerted when cancer-associated fibroblasts (CAFs) — specialized cells in the tumor microenvironment — proliferate and produce increased levels of both collagen and a gel-like substance called hyaluronan.
Experiments in mouse models showed that both collagen and hyaluronan are involved in the compression of blood vessels within tumors, and that losartan can inhibit the production of both molecules by CAFs through reducing the activation and overall density of these cells. Compared with angiotensin-converting enzyme (ACE) inhibitors, which block angiotensin signaling in a different way, losartan and drugs of its class (angiotensin receptor blockers) appeared to be better able to reduce compression within tumors. In animal models of breast and pancreatic cancer, treatment with losartan alone had little effect on tumor growth, but combining losartan with standard chemotherapy drugs delayed the growth of tumors and extended survival.
Source: Massachusetts General Hospital; October 1, 2013.