Taking a “Leaky Faucet” Approach to Chemotherapy

Chemotherapy treatments work best when the drugs are targeted at the location of the tumor. However, it has historically been difficult to get cancer-fighting agents to infiltrate the solid mass of cancer tumors. This is partly due to the fact that high fluid pressure within the tumor reduces the ability of drugs to leak out of the bloodstream and into the tumor’s tissue.

In an attempt to improve the “leakiness” of blood vessels, scientists at the University of California, San Francisco Medical Center have learned that fluid transfer from the blood stream to the tumor increases when certain molecules within blood vessels are blocked.

Specifically, the research team looked at collagen molecules located around blood vessels. Two specific enzymes within this group were found to affect leakiness of blood vessels. These two enzymes are matrix metalloproteinase 14 (MMP14) and transforming growth factor beta (TGFß).

To test the ability to alter leakiness, the team looked at reducing the activity of both molecules, as well as blocking the receptors tied to growth factor. In both cases, the result was improved leakage. Based on studies done with lab mice, it was concluded that leakage into cancer tumors was improved by about 30 percent for larger molecules when steps were taken to improve blood vessel leakage.

While smaller molecules leaked at about the same rate, blockage of MMP14 and TGFß improved the length of time that these molecules stayed within the intended tissue. As a result, this could lead to improved effectiveness and retention of chemotherapy treatments.

Though promising, a few complications need to be addressed before it can be considered for human treatment. For example, finding ways to streamline the passage of pathway inhibitors directly to the tumor tissue is a top concern. According to Ananth Annapragada, an outside researcher from the University of Texas, Houston, “Injecting the inhibitor systemically and hoping it will magically go to the right place might not work out.”

Additionally, any side effects that may result from enhancing the leakiness of blood vessels also needs to be studied before the tactic can be deemed safe for human use.

Resource:

http://www.technologyreview.com/biomedicine/24757/page1/