Using radiation, researchers selectively activate cancer drug

UNC Lineberger researchers led by Andrew Wang, MD, report in the International Journal of Radiation Oncology Biology Physics results from a study of using radiation to activate a new formulation of the drug mitomycin-C in colorectal cancer models.

Using radiation, researchers selectively activate cancer drug click to enlarge Andrew Wang, MD, is a UNC Lineberger member and associate professor in the UNC School of Medicine Department of Radiation Oncology.

An investigational cancer drug is more potent and less toxic with a new formulation that allows it to be selectively activated by radiation treatment, University of North Carolina Lineberger Comprehensive Cancer Center researchers found in a preclinical study.

Researchers report in the International Journal of Radiation Oncology Biology Physics results from a study of using radiation to activate a new formulation of the drug mitomycin-C in colorectal cancer models. They wanted to test whether selective activation of the drug in tumors using radiation would make the drug more potent and spare normal cells from the drug’s toxic side effects.

“The main issue of mitomycin-C is toxicity,” said Andrew Wang, MD, a UNC Lineberger member and associate professor in the UNC School of Medicine Department of Radiation Oncology. “This new drug formulation may make this regimen safer and more effective.”

The researchers believed the formulation would reduce the drug’s toxicity because drug would be preferentially released where physicians choose to use radiation treatment, said Joseph Caster, MD, PhD, co-chief resident in the UNC School of Medicine Department of Radiation Oncology.

Caster said a special link between the outer coating of the drug and the compound is the key to selective activation of the new formulation. They hypothesized that in response to radiation, the tumor cells would emit agents that could cleave the links between the drug and the outer coating, thereby releasing the drug.

For the study, the researchers worked with the company LipoMedix to study the investigational drug formulation, which is known as Promitil, in combination with radiation treatment. The company is working to develop Promitil as a treatment for colorectal cancer. The drug is a new formulation of mitomycin-C, a common chemotherapeutic for the treatment of anal and bladder cancers.

The UNC Lineberger-led team tested the investigational commercial formulation in colorectal cancer models. They found that with radiation, the investigational formulation was less toxic to blood and hair cells outside of the tumor than the compound alone. The new formulation was better tolerated in laboratory models of colorectal cancer human tumor tissue. By combining radiation treatment with the new formulation, they significantly prolonged the delay of tumor growth in two different laboratory models, while the drug alone or with radiation did not significantly delay the cancer’s growth.

In addition to Caster and Wang, other authors on the study include: Xi Tian, PhD; Samuel B. Warner; Kyle T. Wagner; Tian Zhang, MD; Patricia Ohana, PhD; and Alberto A. Gabizon, MD, PhD.