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Designing a personalized treatment for cancer

Yi-Shan Yang
Department of Radiology
Stanford University
June 2003

In past decades, scientists have put tremendous efforts into discovering an efficient way to treat cancer. While current treatments (like chemotherapy) are effective, most of the time they are too powerful - by targeting both normal and cancer cells. One key feature of cancer is that cancer cells have significantly more blood vessels compared to normal cells. These blood vessels grow aggressively, allowing the tumor to expand rapidly. My research explores the behavior of genes related to blood vessel growth in cancers. Scientists can then design new medicines to turn off the production of those genes. This treatment will suppress the blood vessel development, and thus the tumor growth. Since different cancers may have different genes produced at a high level, cancer treatment can be personalized and specified for those genes only. This approach is intended to be a more efficient and specific method compared to current treatments.

Two instruments and a chemical solution are used in my research. The first is a Magnetic Resonance Imaging (MRI) scanner. MRI is a technique that generates images when an object (a brain, a knee joint, or an animal) is scanned. A MRI scanner has a very high resolution, so the detailed structure, such as the organs of an animal, can be observed from the image. Since my research focuses on the blood vessel development of tumor, I also use a contrast agent when generating the MRI images. This solution makes the image of blood vessels brighter, and easier to detect. The second instrument I use is called a GeneChip System. A gene chip is a small piece of glass that has millions of small molecules attached to it. These molecules represent thousands of genes for a specific species, such as yeast, mice, or human.

In my research, I injected the cancer cells underneath the thigh skin of mice. Once the cells grew to about 1 cm in diameter, I injected the contrast agent to their blood vessels and scanned those animals in a MRI scanner. The contrast agent travels through the blood vessels, and makes the MR images brighter. I separated these brighter areas from darker ones, and isolated a special component, called the messenger RNA (mRNA), from the cell nucleus. The mRNA contains all the genetic information of the cancer cells. Next I used the GeneChip system to analyze the mRNA. This instrument generates signal intensity for each gene contained in the mRNA. The stronger the signal is, the higher level the gene is produced in the cancer cells. I repeated the above procedures for the samples that show bright or dark MR images for 54 mice. For each sample, I obtained a list of genes with intensities indicating their production level.

Since the purpose of my research is to find out what genes are related to blood vessel growth, which is reflected in the bright area of the MR image, I have to find out the genes that are produced at a high level only in the bright area. In other words, genes that are produced at a high level in both bright and dark area would have no use for me as they are not related to blood vessel growth. Thus, the production level of the genes from the dark area in the MR images serves as the baseline. By comparing the production level of the genes in the bright area to the dark area (baseline), I obtained a list of genes that have high level of production only in the bright area.

Next I did an intensive literature search for those genes to understand their functions and their roles in cancer development. I discovered that most of those genes are related to cell growth, blood vessel development, and communication between the cells. The next step of this research is to develop medications that can recognize these genes and shut down their production. By this approach, the blood vessel growth can be suppressed and the cancer can be treated. It is also critical to extend these procedures to different cancer types, because the high activity genes will be very different in different cancers.

The results from this research are significant because I have demonstrated that genes related to blood vessel growth can be monitored with the brightness of the MR images of the tumors. In the future, patients with cancer can take an MR scan with the contrast agent. Based on the brightness of the MR images, the doctor can know what genes may have a high production level. Then a proper medication can be used to shut down their production. It can make the cancer treatment more efficient and accurate, and can avoid the killing of normal healthy cells that occurs with current treatments.