Though the effort took more than a decade, Folkman's lab managed to track it down. Another inhibitor was found by a combination of luck and scientific detective work when a fungus blew into the lab.
What seemed like a disaster, threatening to contaminate everyone's experiment, turned out to contain a molecule that inhibited the growth of blood vessels. Another approach created a new use for the notorious drug Thalidomide, which was discovered to inhibit new blood vessel growth.
Thalidomide is a tranquilizer that caused severe birth defects when prescribed in Europe in the early s as a morning sickness medication for pregnant women.
It is now being used in clinical trials to treat some cancers. In Folkman suggested a startling new place to look for angiogenesis inhibitors: the tumor itself. Why would a tumor, which stimulates new blood vessel growth, produce an inhibitor of blood vessels? The answer not only led to the discovery of a potent inhibitor of angiogenesis, but also solved a century-old medical puzzle.
It was long known that in some rare cases of cancer, the surgical removal of the primary tumor would be followed by a rapid growth of small metastases that had spread to other locations. Could the tumor itself be secreting a molecule that kept the metastases at bay? When the tumor was removed, did that also remove the inhibitor? After a series of ingenious experiments involving the collection and analysis of large amounts of mouse urine, such inhibitors were found: Endostatin and Angiostatin, natural proteins that prevent tumors from stimulating new blood vessel growth.
Judah Folkman started his long journey as a lonely warrior in the battle against cancer. Today hundreds of labs around the world are working on angiogenesis. They are frequently built and repaired. The process is very organized and efficient. Examples include wound healing and the menstrual cycle. Tumors need blood vessels to survive, but the blood vessels are abnormal, twisted and leaky. This can lead to treatment resistance and the spread of cancer.
Abnormal angiogenesis is not limited to cancer. Other diseases, including macular degeneration, a progressive eye disease, are linked to abnormal development of blood vessels. Like all cells, cancer cells require a constant supply of nutrients and oxygen in order to grow and divide.
Without an adequate blood supply tumors will not grow. Tumors produce factors that stimulate the formation of blood vessels to provide them with the food and oxygen they need. The process of blood vessel formation is termed angiogenesis. This process is a very active area of research in cancer treatment for several reasons.
The treatments should have low toxicity. Angiogenesis occurs at high levels during fetal development, the menstrual cycle and in wound healing. The treatments might be expected to interfere with these processes but should not harm most normal dividing cells. The treatments are not designed to directly attack the cancer cells. The targets of several of these treatments are normal processes controlled by normal cells such as the cells that form blood vessels , not the tumor cells themselves.
The high mutation rates of cancer cells that often render chemotherapy ineffective will not interfere with these drugs. This drug is actually a naturally occuring protein that is derived from the cleavage of a larger protein, plasminogen. Angiostatin inhibits the growth of blood vessels in tumors and has been shown to inhibit metastasis of tumors in animal models.
This drug is is no longer in clinical trials 7 8 9. This interactive video includes 11 slides. For each slide the students view, they should write down a summary of what is taking place during the development of each cancer cell.
By the end of the slide show, the students should have a full summary of how a cancer cell grows. Once they are finished with the interactive, the students can click on Possible Cancer Treatments.
Here, the students can chose 2 possible cancer treatments and summarize what they are and how they may help a patient with cancer. This site goes through a step-by-step process of cell growth with a video as well as a description of each picture. Collect the summaries from the students and collect it as a class work grade.
This should be used more as a review or reinforcement activity.
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