Using proteomics technology developed by Lance Liotta and Emanuel Petricoin, researchers are testing whether a drug used for malaria is also effective for treating pre-invasive breast cancer.
George Mason University's Center for Applied Proteomics and Molecular Medicine and the Inova Breast Care Institute are collaborating on the project, which is aimed at investigating the effectiveness of chloroquine as a treatment for breast cancer before it becomes invasive. A three-year clinical trial has begun that will eventually include 90 women with ductal carcinoma in situ, or DCIS. The trial is called Preventing Invasive Breast Neoplasia with Chloroquine.
In DCIS, cancer cells have formed in the milk ducts, but they have not yet become invasive and spread throughout the breast. Once the cancer reaches that stage, it can be fatal.
Petricoin says the technology, "reverse-phase protein microarray technology," which he developed in collaboration with Liotta, was used by Virginia Espina, a senior research professor at CAPMM, to discover protein alterations in a process called autophagy. Those changes then led Espina to "postulate that a drug, chloroquine, could be potentially effective in killing the premalignant cells — stopping everything before the cells turn invasive."
The technology, he adds, will not be used in the trial to select patients for therapy "but will be critical in looking at the DCIS cells pre- and post-therapy, and then hopefully [Espina] can identify specific protein pathway markers to predict best responders to chloroquine."
Autophagy is "very involved in the survival of DCIS," Kirsten Edmiston, the trial's principal investigator and medical director for cancer services at Inova Health System in northern Virginia, said in a statement. "In preclinical work, our team found that if we block autophagy in DCIS cells with chloroquine, that it kills the cells so that they're not able to become invasive."
In the trial, DCIS patients will be treated with chloroquine before they receive standard-of-care surgery. A patient's breast tumor will be measured by MRI, and tissue samples will be sent to CAPMM for analysis. Depending on the patient's profile, treatment will combine chloroquine with tamoxifen.
After treatment, the tumor will be measured again to determine whether it has shrunk. The patient will then proceed with surgery and follow-up therapy as necessary.
"We believe that the treatment will kill the DCIS cells before they become invasive and shrink the size of the DCIS," Edmiston says. "We may be able to prevent someone from needing a mastectomy and offer them breast-conserving surgery."