Scientists know that normal stem cells have two critical features, the ability to self-renew and the ability to resist toxins through transporters that pump away foreign substances. According to Dr. Donnenberg, this very knowledge may provide a promising new paradigm to understanding the growth and spread of cancer.
The project will examine a subset of highly malignant cells in breast cancer tumors, which resemble adult stem cells, and may be responsible for the development of breast cancer. Referred to as tumor stem cells, these cells are hypothesized to give rise to rapidly growing cells that form the bulk of a cancerous tumor.
"Much like a seed is necessary for the growth of a plant, we believe that tumor stem cells exist at the heart of a tumor and perpetuate the growth of cancer," explained Dr. Donnenberg, who is assistant professor of surgery at the University of Pittsburgh School of Medicine. "These cells appear able to induce the growth of cancer through characteristics similar to those of stem cells in that they are slow-growing, self-renewing and contain powerful drug-resistant pumps that withstand toxic substances such as those administered during chemotherapy."
In the study, Dr. Donnenberg and colleagues will examine breast cancer tumors and surrounding tissue for cells expressing both markers associated with normal stem cells and breast cancer cells. They expect to find that early tumor stem cells will express drug-resistant pumps that can survive treatment while the majority of cancer cells, forming the mass of a tumor, will be destroyed by conventional chemotherapy. Follow-up studies on breast cancer patients who have undergone chemotherapy will help determine whether these tumor stem cell-like cells are still present following treatment.
"We believe that current breast cancer therapies, while effective against the bulk of a tumor, may be focused on targeting the wrong cells and, as a result, are unable to effectively protect against cancer spread and recurrence," said Dr. Donnenberg. "Findings resulting from this project may indicate the need for a critical adjunct to conventional therapy – one that directly targets tumor stem cells and the activity of their drug-resistant pumps."
The project is supported by the BCRP's Era of Hope Scholar Award and is one of only five in the country awarded in fiscal year 2004. The award was established by the BCRP in 1992 to promote innovative research directed toward eradicating breast cancer. The award is intended for exceptionally talented, early-career scientists who have demonstrated a strong potential for leadership in the breast cancer community.