AsianScientist (Jun. 6, 2011) – Scientists at the Walter and Eliza Hall Institute have discovered a key molecule needed to kill the blood vessels that supply tumors.
The research team found that for anti-cancer therapies against tumor blood vessels to work, the death-inducing molecule Bim is required. The findings were published today in the Journal of Experimental Medicine.
The growth of solid tumors such as lung cancer, breast cancer, and melanoma depends on nutrients and oxygen being provided by the tumor blood supply. Cancer cells encourage the growth of blood vessels to feed a tumor by producing the hormone-like protein, vascular endothelial growth factor (VEGF).
Led by Professors Jerry Adams and Andreas Strasser, the researchers showed that VEGF produced by tumors blocks production of Bim in the cells that line the tumor blood vessels.
In experimental melanoma, lung cancer, and breast cancer models, increased levels of Bim were found in the cells lining the blood vessels when VEGF was depleted by anti-angiogenic drugs, ultimately killing the blood vessel cells. VEGF depletion reduced the number of blood vessels in tumors, making the tumors shrink.
In mice, however, in which the blood vessels do not express Bim, VEGF depletion did not affect the number of tumor-associated blood vessels, and tumors grown in Bim-deficient mice did not respond to anti-angiogenic treatments.
These findings suggest that strategies for treating tumors by attacking the tumor blood supply could be optimized by incorporating BH3 mimetic drugs that act like Bim at a molecular level.
“BH3 mimetics may have two beneficial effects in cancer therapy. Our previous research had showed they can directly trigger death in tumor cells, particularly when the tumor is also attacked by chemotherapeutic drugs. We now think BH3-mimetics could also impact tumor cells indirectly by killing endothelial cells within tumors,” Strasser said.
According to Strasser, a three-medication combination may provide a promising new approach to the therapy of solid tumors: a drug that specifically targets the tumor cell, an anti-angiogenic agent to impair the tumor blood vessels, and a BH3 mimetic to assist the action of the other two drugs.
——
Source: Walter and Eliza Hall Institute.
Disclaimer: This article does not necessarily reflect the views of AsianScientist or its staff.
