Blocks the blood vessels that feed them and starves the cancer
These days, a new drug has been released on the market in the United States that proves for the first time one of the most important ideas for the treatment of cancer - "starving" the tumor by blocking the blood vessels that feed it as a way of treating humans. The idea was conceived by Prof. Yehuda Folkman in the 70s, but its execution has since gone through upheavals. The drug, which went on the market at the end of February, is the first treatment of its kind aimed at preventing the formation of new blood vessels around the tumor and into it, which succeeded in delaying the development of a cancerous tumor in humans. The American pharmaceutical company Genentech received the approval of the American Food and Drug Administration (FDA) for the use of the drug, which was given the name Avastin. The biomedical community sees the event as a significant breakthrough in the treatment of cancer.
According to Folkman, a researcher at Harvard University, a tiny cancerous tumor can be located within the tissue in a dormant form without growing. At a certain point there is a turning point in its development, which is manifested in the acquisition of the ability to attract blood vessels that supply it with oxygen and nutrients and enable its massive growth. The creation of blood vessels around the tumor and into it - a process known as angiogenesis - is what enables the transition from a small and dormant tumor to a wild and violent tumor that spreads throughout the body. Folkman and his team succeeded in isolating natural substances that inhibit the formation of blood vessels and showed that they can dramatically shrink malignant tumors in mice.
It was in 1998. The impressive results received a tremendous media response, but it grew cold because the successful experiments in mice did not prove themselves in humans. But the scientific community and pharmaceutical companies did not give up. There were two reasons for this: Folkman's concept was very attractive, mainly due to the logic built into it, but the main reason was the continuous failure in dealing with cancer. At the end of last month, as mentioned, the new drug, Avastin, was released, which succeeded in inhibiting cancer growth in humans.
Avastin is an antibody that is uniquely directed against one of the key factors that stimulates the formation of new blood vessels - a substance called VEGF. VEGF is responsible for creating a blood vessel network in the majority of cancerous tumors. When the cancerous tumor goes from a dormant state to violent growth, it secretes large amounts of VEGF, which stimulates the formation of blood vessels around it and these supply it with oxygen and nutrients and allow it to continue to develop. The approval of the American Drug Administration was based on clinical trials conducted in more than 900 patients with generalized colon cancer, in various medical centers. The patients were divided into two groups. One group received Avastin plus chemotherapy, and a control group received only chemotherapy.
The assumption was that the combined attack would give the best result. In all the anti-cancer treatments developed in the last decades, the target was the tumor cells. But the tumor cells as a target of attack proved to be problematic. They are genetically unstable, and over time they accumulate many mutations that make them resistant to treatment. The use of substances that inhibit blood vessel formation is directed against the endothelial cells lining the blood vessel wall, around which the new blood vessels are organized. Endothelial cells, in contrast to cancer cells, are genetically stable, so the risk of them developing resistance to chemotherapy agents is low, and they can be just as good a target as the tumor cells. The treatment that combines Avastin and chemotherapy works against both types of cells.
The clinical trials showed that the life expectancy of the patients who received the combined treatment was five months longer than that of the control group. "The results, even if they don't seem dramatic, are significant and constitute an important breakthrough," says Prof. Eli Keshet from the Hebrew University School of Medicine, who is involved in VEGF research. "The very feasibility of a new cancer treatment, which proves itself in humans, is an important foundation on which improvements will be built in the future. Volkman compares this achievement to the achievement of the Wright brothers, who in their first flight stayed in the air for only 12 seconds, but thereby opened the era of aviation. Beyond that, it is impossible to ignore the fact that five additional months of life with a good quality of life is no small thing for cancer patients. Five months was an average response, and in practice there was variation between the patients in the degree of response to Avestin. The question is why some people respond well to the drug and others respond less. If we manage to understand the reasons for the variation in the effectiveness of the response to the drug we can use this knowledge to improve the treatment. These are open questions that require further research."
In the future, according to researchers involved in the development of the combined treatment, the treatment will include relatively small doses of chemotherapy accompanied by substances that inhibit the formation of blood vessels. In the treatment, which received the name "metronomic dosing", the patients will receive the drugs at fixed time intervals without interruption. The current approach to cancer treatment is to kill as many cancer cells as possible using a high dose of drugs and then give a grace period to restore the damage done to the healthy cells. However, during this time, the blood vessels around the tumor also recover and a new, more violent tumor develops, which does not respond to drugs. In the "metronomic dose" they will use low and continuous doses of the combined treatment without a "break" period, with the assumption that the damage will not only be to the tumor but also to the endothelial cells, and when these are eliminated, the tumor will shrink.
In the future, clinical trials are planned in additional types of cancer and also in patients with colon cancer that has not yet spread in the body.
