The Walter and Eliza Hill Institute, Molecular Genetics of Cancer and Haematology found that Bim can kill the blood vessels that feed oxygen and nutrients to cancerous tumors in breast and lung cancers. By increasing levels of Bim in blood vessel cells, the blood vessels begin to die and cancerous tumors are no longer supplied by nutrient rich blood.
The Bim molecule has an association with the protein, vascular endothelial growth factor (VEGF) that stimulates endothelial cells in the walls of blood vessels. When the levels of VEGF are high in cells, the Bim molecule is blocked. Cancerous tumor cells encourage the production of VEGF and this leads to a decrease in Bim in the tumor blood vessel cells. Conversely, if VEGF production is decreased, Bim levels can increase, which can lead to death of blood vessel cells and the overall death of the entire blood vessel.
When scientists from the Walter and Eliza Hill institute decreased VEGF levels through the use of anti-angiogenic drugs (drugs that reduce growth of blood vessels), the number of tumor blood vessels decreased and the tumors started to shrink in size. However, the active version of Bim must be present in blood vessel cells for VEGF levels to decrease. This was determined in mice that did not actively express Bim. When levels of VEGF were decreased, the number of tumor blood vessels did not correspondingly decrease.
Other drugs that mimic the mechanism of Bim may also have promise as cancer fighting treatments. These drugs are known as BH3-mimetics that also reduce the blood supply to cancerous tumors. BH3-mimetics have also been shown to directly activate tumor death when used in combination with chemotherapeutic drugs and BH3-mimetics which may kill the tumor’s endothelial cells.
Hence, multiple steps can be incorporated into cancer treatments that take into account drugs that directly affect the tumor cells, anti-angiogenic drugs that reduce the blood supply to the tumor by impacting the blood vessel cells, and BH3-memetics that assist the anti-tumor drug and the anti-angiogenic drug.
Beyacizumab (Avastin®), an anti-angiogenic drug, has been approved by the U.S. Food and Drug Administration.