research, Kim, HER2, breast, gene
Sung-Woo Kim's research on functional genomics at the Alberta Cancer Board
Functional Genomics -- New Way to Study Cancer Cells
Dr. Sung-Woo Kim was finishing his doctorate in Halifax when his father died of cancer. Although Kim’s work at the time focused on obesity, he knew that his post-doctorate research would explore the mysteries of genes and try to answer some of the most fundamental riddles about what happens when cancer attacks the body.
Ten years later Kim is in Calgary setting up a functional genomics laboratory in the new Health Research Intervention Centre.
Kim and his research team are investigating the building blocks of heredity. Genes direct the production of RNA, ultimately determining everything from the shape of a plant leaf to the texture of your hair. There are about 23,000 genes in the human body and until recently research focused on understanding individual genes and their actions.
“We know how some of them function individually, but not how whole genes in the cells respond to cancer - that’s what’s called functional genomics. We are using cutting edge technology to see the big picture.”
Kim’s team suppresses as many as 7,000 genes at once to see the impact on how cancer behaves. The cells are then treated with a cancer drug. More than 80 per cent will die. The ones that survive will be “mined” for further study.
Focusing on breast cancer, the surviving cells may explain why some women don’t respond to cancer drugs, just as some people can develop resistance to antibiotics. Kim points out that almost one third of women with breast cancer overproduce a protein called HER2, which is normally responsible for helping cells grow or differentiate. But in some cases, cells are given a signal that leads to hyper-growth, producing much more HER2 than necessary, which develops into a breast cancer that is more aggressive and less treatable than other forms.
Herceptin has been an effective targeted therapy for many women by binding to the HER2-producing cancer cells and blocking them from uncontrolled growth. But the drug isn’t effective for every woman. “The genes that survive - how can they ignore this drug?” asks Kim.
After finding the explanation, the next challenge is discovering a way to inhibit the drug-resistant genes. The answers could lead to more effective targeted treatments.
Kim’s lab is tackling related questions about other genes, the so-called tumour suppressors. In normal cells, these genes keep cells from becoming malignant, but if inactivated the cell’s growth is essentially unchecked, increasing the risk of cancer. Kim identified a tumour suppressor called Tid1 and discovered how it works to cause the death of cancer cells. His expertise in mouse models has led to the development of a conditional K/O (knockout mouse). The mammal is bred without the Tid1 gene in the breast, helping Kim and his team find out more about how Tid1 works in vivo (within the living body), particularly how its deletion promotes breast tumour development.
Kim believes that the genome-wide approach will accelerate the search for a cure for cancer, and that increased collaboration between the lab and clinical treatment will ultimately remove roadblocks and save vital time.
Sung-Woo Kim is the Principal Investigator for the Southern Alberta Cancer Research Institute and the Canadian Research Chair Tier II for Cancer.
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