The message I want to convey is that our work from mice and from humans has shown that if we give anti-angiogenic therapy, two things happen: We kill blood vessels and we make the remaining vessels better and closer to normal vessels in their structure and function—a condition referred to as normalized.
This normalization concept begins to explain why the combination of anti-angiogenic therapy with chemotherapy and/or radiation therapy leads to improved outcomes in colorectal and lung cancer patients. And these results begin to explain why anti-angiogenic therapy alone does not lead to increased overall survival of patients—because we cannot destroy all of the blood vessels of tumors with Avastin or other drugs that target VEGF alone without undue harm to the normal blood vessels.
This concept of vascular normalization is relatively new and it is going to take some time before we can exploit it completely. We are conducting a number of clinical trials at MGH to fill this gap in our knowledge. Questions that we are asking include: How long does the window of normalization last in different tumor types in response to different drugs? When does this window open and when does it end? Is normalization reversible? Can we detect it with various imaging techniques? Can we detect it with molecular and cellular biomarkers in the blood or urine of patients? Can we select patients who would respond to these types of therapies better? How can we use this knowledge to combine anti-angiogenic drugs with conventional therapies (for example, chemo or radiation therapy) and novel targeted therapies (for example, Herceptin)?
Our hope is that we can take the data from our ongoing trials, learn from them, and extend survival not by two to five months, as it is for many patients taking anti-angiogenic therapies today, but by 10 or 20 to 50 years.