BU chemists receive grant, research cancer-killing drug

Taipei, Taiwan, graduate student Chen-Ming Lin and Nepal doctoral candidate Laxman Devkota work in a fume hood equipped for chemical synthesis and compound purification.Carlye Thornton | Lariat Photo Editor
Taipei, Taiwan, graduate student Chen-Ming Lin and Nepal doctoral candidate Laxman Devkota work in a fume hood equipped for chemical synthesis and compound purification.
Carlye Thornton | Lariat Photo Editor

By Viola Zhou
Reporter

Chemists at Baylor received a $900,000 grant to support research on drugs that kill cancer cells but leave healthy cells unhurt.

Dr. Kevin Pinney, professor of chemistry specializing in chemical synthesis, and Dr. Mary Lynn Trawick, associate professor of chemistry and biochemistry, lead the team developing and studying compounds that target cancer tissues. The three-year grant they received this fall was from the Cancer Prevention and Research Institute of Texas.

Pinney said each compound contains two parts, a small potent molecule that hits all cells and an inactive molecule called prodrug that prevents the drug from acting against healthy cells.

Pinney said in theory, when the drug enters a tumor, where the fast-growing cells create a low-oxygen environment, the prodrug will cleave off and the anti-cancer molecule will be delivered to hit the cells.

Trawick said her group is now evaluating whether the compounds can effectively target cancer cells without hurting healthy cells.

“We culture breast cancer cells under normal oxygen levels and under hypoxia, which means low-oxygen levels,” she said. “And we compare how many cells are killed by these potent agents.”

She said the group has received promising preliminary results with some of the compounds, but it is hard to predict the results of the following experiments.

Trawick said their collaborator, Dr. Ralph Mason of the University of Texas Southwestern, has verified some animal models have hypoxic regions in the tumor. The animal models will be used to test the compounds in the future.

She said to find compounds that target only tumor cells is the biggest challenge in cancer drug development. Prodrugs that are activated under hypoxia have the possibility to make cancer drugs very selective.

“A high percentage of advanced breast cancer has regions of low oxygen, while normal cells don’t,” she said. “It will also be applicable to other cancers.”

Pinney said the drugs are still very far from entering a clinical trial and the market. The institute funded their research because it has potential to help cure cancer.

“They think this strategy of targeting hypoxia with the particular molecules could be promising in the sense that the pre-clinical studies they are going to fund could eventually translate to something that would be clinically applicable,” Pinney said.

The research team is also working on other tumor-targeting methods. Pinney said the team received a $1.46 million grant from National Institute of Health in 2009 for developing a compound that targets cancer cells by constraining their blood flow and oxygen supply.

He said historically, the molecules used in cancer chemotherapy hit both healthy and tumor cells, but the last 10 to 20 years have seen a worldwide focus on trying to target therapies selectively toward tumors.

“What we are doing fits in the overall umbrella,” he said. “We are not the only people doing this. We fit into a small piece of that adventure.”

Pinney said he has been at Baylor for 21 years and about 95 percent of what his team does is cancer drug research.

“It’s a staggering worldwide problem that affects so many people, either directly or through their family members and friends,” Pinney said. “It’s fair to say as a strong Christian I always feel God calling me in this direction to work in this area.”

Trawick said she has been collaborating with Pinney for over a decade and she finds cancer drug research both challenging and interesting.

The research they are doing involves a large team of collaborators and students, Pinney said. In the team’s laboratories, doctoral candidates, graduate students and undergraduates work together on the projects.

“It’s an environment where there is a lot of exchange of ideas and people are learning from each other and being inspired by each other,” Pinney said. “I rely on those folks for really making things happen. They are the ones taking some of the initial ideas, turning them into things that are tangible and coming up with new ideas.”