A team of scientists co-led by Sui Huang, MD, PhD, associate professor of Cell and Developmental Biology, found that an experimental drug called metarrestin significantly suppressed metastatic tumors and extended tumor bearing animal survival without prompting any adverse side effects.
The study, published in Science Translational Medicine, suggests that metarrestin could be an effective chemotherapeutic tool used in combination with existing drug therapies to further reduce metastasis and cancer recurrence, ultimately extending patient survival.
According to Huang, the inner workings of cellular processes behind metastasis still aren’t well understood. Although many therapies are available for patients with metastatic cancer, including chemotherapy and radiation, they can attack both cancer cells and healthy cells, which can contribute to less than ideal patient outcomes after cancer surgery. Although immunotherapy and targeted therapy have efficacy against a narrow group of patients, the efficacy often is not long lasting.
“The objective of this study was to find a therapy that was more selective against cancer so that it didn’t affect everything else. That’s why we were looking for a phenotypic marker that only exists in cancer cells and not in normal cells,” Huang said.
In the current study, Huang and colleagues used the perinucleolar compartment (PNC)—a complex nuclear structure almost exclusively associated with cancer cells—as a phenotypic marker to evaluate 140,00 compounds and determine which compound most effectively targeted PNCs in advanced prostate cancer cells. Huang first associated PNCs with cancer cells and cancer progression over two decades ago.
Using pancreatic cancer mouse models, the scientists found that metarrestin prevented further metastasis by inhibiting cancer cells’ ability to grow and spread. Mice treated with the compound also had a more than doubled life expectancy without any detectable adverse effects, such as organ toxicity. Huang said the ultimate goal is to use metarrestin in clinical settings in combination with existing therapeutics to give patients a better quality of life.
As for next steps, Huang said that study co-author Udo Rudloff, MD, PhD, an investigator with the Thoracic and Gastrointestinal Oncology Branch at the National Cancer Institute, has prepared to submit an Investigational New Drug application to the Food and Drug Administration to begin testing the drug in pancreatic cancer clinical studies.
Huang said she is also interested in potentially testing the drug in future prostate cancer trials at Northwestern and possibly breast cancer trials.
Funding for the study was provided by the National Institutes of Health, and IDP, H and V foundation funding from the Robert H. Lurie Comprehensive Cancer Center of Northwestern University, of which Huang is also a member.