U-M research team seeks to improve breast cancer detection
Researchers at the University of Michigan are developing a new diagnostic pill that improves conventional detection methods and reduces the overtreatment of breast cancer. The U-M research team, led by Greg Thurber, chemical engineering assistant professor, is refining an oral pill that dissolves in the bloodstream and illuminates tumors under infrared light.
According to Thurber, many women who have breast cancer tumors would never suffer from the disease but are treated anyway. Mammography, a common form of breast cancer detection, determines the existence of a tumor but not if the tumor is cancerous or benign. Chemicals in the new pill are able to bind to cancerous tissue and light up under infrared light to inform physicians where cancerous tumors are located.
Thurber says that knowing information at the molecular level is at the core of effective cancer detection.
“We've known from decades of research in cancer biology that it's really a molecular disease, so what's nice about our approach is that you're actually getting molecular information,” Thurber said.
The pill is an alternative to mammograms or other methods such as magnetic resonance imaging and ultrasounds. According to Thurber, mammograms can sometimes be inaccurate, as they may miss tumors in women with dense breast tissue.
Thurber believes his team’s method would be useful at spotting tumors in patients where mammograms don’t work well.
"In the short term, we wouldn't be necessarily replacing a mammogram; we would be trying to provide more information to the physician so that they could make better decisions from the results they would get from both this imaging and a mammogram,” Thurber said. “Long term, the idea would be to completely replace (mammograms) because there are many challenges with mammograms that we believe our approach can help overcome.”
Providing more accurate screening results is also comforting to patients. Rackham student Sumit Bhatnagar assisted with the research for the project and emphasized the importance of reducing the overtreatment of breast cancer.
"When you have a lot of patients that have to go through chemotherapy and all these procedures that are not required, it leads to a loss of quality in life for a lot of these people,” Bhatnagar said. “So that's something that can be avoided in the screening stage that would be preferable.”
The pill is taken orally and dissolves into the bloodstream, just like food, says Thurber. The carefully-designed molecules are distributed throughout the body and bind onto breast cancer cells. After a few days, a physician looks for tumors by shining a near-infrared light on the breasts.
Pharmaceutical sciences professor David Smith assisted Thurber’s team with the research. According to Smith, one of the team’s challenges was assuring the molecule was correctly absorbed by the body. The team had to design a molecule that was soluble enough to be absorbed into the bloodstream, but also greasy enough to pass through a tumor cell’s membrane.
“It has to have the right chemical structure to have selectivity for cancer cells and not normal regular cells,” Smith said. “So you can imagine getting all those qualities in one molecule is not so easy.”
According to Bhatnagar, the research team created a range of different imaging agents with varying properties to see which combination of properties would work best in the body.
"We did cell experiments and plate experiments to eliminate a few of these, so based on certain properties we narrowed it down from the five or six to about three, which we then tested in mice to see which one was the one we could get the highest amount of into the blood,” Bhatnagar said.
With successful results on mice, the team is looking to expand the method for not only other types of cancer, but other diseases as well. According to Bhatnagar, the team is testing the molecule for detection of rheumatoid arthritis.
According to Thurber, the team’s next steps are to conduct toxicity testing required by the U.S Food and Drug Administration to ensure components of the molecule remain safe when they are linked together and no unexpected toxicity is produced. The team would also like to pursue testing on larger animal models, to guarantee the molecule works well in larger models of breast cancer.
"Once those studies are done, with the right collaborators and industry and academia, then we would push forward for a clinical trial,” Thurber said.