New Investigator Profiles

Sonoko Narisawa, Ph.D. and Ling Jong, Ph.D.

Sonoko Narisawa, Ph.D.: Searching for the molecule that lets breast cancer spread to bone

Why does breast cancer often spread to a woman's bones? Sonoko Narisawa, Ph.D., was a post-doctoral researcher at The Burnham Institute in La Jolla when she came up with an idea for a research project that could help answer this question. The project would tap her experience in both bone biology and cancer research. A 1998 New Investigator Award from the California Breast Cancer Research Program allowed her to develop and implement the project.

"When I was a post-doctoral researcher, my supervisor decided which projects I worked on. The New Investigator Award gave me total freedom to pursue my research hypothesis," says Dr. Narisawa. In the first step of metastasis to the bone, breast cancer cells circulate in the blood, and then attach themselves to bone marrow. "Using the method I developed, I want to find the molecule(s) involved in breast cancer metastasis to bone," Dr. Narisawa says. She began to search for key molecules.

Her research established the methodology for finding the "bone homing" molecule or molecules. She is currently preparing a paper based on this research for submission to a scientific journal.

Dr. Narisawa, now a Research Associate at The Burnham Institute, is also submitting grant applications to fund the next steps in her research. Once the key molecule is found, the molecule itself or a part of the molecule could be used to block the receptor molecule on the bone marrow cells, leaving nowhere for breast cancer cells to stick. The bone homing molecule coupled with an anti-cancer drug may have potential to be used to target cancer cells already metastasized to bone.

Dr. Narisawa, originally from Japan, has chosen to work in the US. She believes the United States gives much greater opportunities to women scientists. She became interested in cancer research when her father and several other family members died of cancer.

"My hobby is doing science in the lab," she says. "My long term goal is to contribute to the improvement of human health. I often need to spend long hours in the lab, but for me, it's fun."

Ling Jong, Ph.D.: Toward a Drug that Prevents and Treats Breast Cancer

Ling Jong had an idea. She wanted to modify a molecule found in broccoli, to see if she could make its breast-cancer-preventing action more potent.

A Ph.D. chemist at the Menlo Park research institute SRI International, Dr. Jong was assisting other more senior researchers at the time. She couldn't just try out her idea. She needed a grant to fund the laborious synthesis of compound after compound, each with a slightly different molecular structure, in order to improve the anti-cancer activity while preserving the safe biological profile. She also needed funds for a biologist. The biologist would test the new compounds on breast cancer cells growing in lab cultures, to see which compound best inhibited cancer cell growth.

"It's impossible for a really junior researcher to get a grant from the National Institutes of Health. You need to be much more established and famous," says Dr. Jong.

A 1998 New Investigator Award from the CBCRP gave her the opportunity to test her idea. Today, Dr. Jong's most promising compound is on track to become a drug for both prevention and treatment of breast cancer.

"Most compounds fail to become drugs because they are toxic. I wanted to start with a natural compound, something people have been eating for thousands of years. That way, there's less chance of toxicity," she says.

Dr. Jong modified Indole-3-carbinol to improve its anti-cancer activity. This substance, found in broccoli, cauliflower, and other related vegetables, is known to prevent breast cancer. However, eating broccoli won't work to treat breast cancer, because Indole-3-carbinol is not potent enough. So Dr. Jong searched for chemical variations of Indole-3-carbinol that would work most powerfully at the lowest possible dose. Once she found the compound that was most effective against breast cancer cells in the lab, she tested it on mice. She found that low doses prevented tumors and high doses stopped the growth of tumors, with no toxic side effects.

"We're especially excited because this compound works both against estrogen-dependent tumors and estrogen-independent tumors," she says. "Estrogen-independent tumors are harder to treat. Very few other compounds inhibit them."

The CBCRP gave Dr. Jong a second grant in 2001 to push forward the process of turning this promising compound into a drug. She has applied for a patent on the new compound, and the National Cancer Institute (NCI) has encouraged her to apply for funds for a Phase I clinical trial, the first step in testing her candidate breast cancer drug in humans.

Today a Senior Organic Chemist at SRI International, Dr. Jong credits the CBCRP New Investigator Award for establishing her breast cancer research career. Before she received the CBCRP grant, she assisted other more senior chemists with research into various types of cancer. She was part of a team that created the molecule that has been developed into the drug Targretin, which is used to treat a type of lymphoma.

But Dr. Jong wanted to specialize in breast cancer. "I worked very closely with a colleague whose wife got breast cancer. It's one thing to read the statistics, but it's another thing to see breast cancer in someone close to you. It scared me, and gave me an urgency to do research to help cure this disease," she says.

For now, Dr. Jong is very busy doing research necessary to prepare to test her candidate drug in humans. "The New Investigator Award allowed me to pursue research when I had very limited data, just some computer modeling analysis to support my theory," she says. "Now, it may result in a breast cancer drug in the future."