New Therapeutic Approach May Stop Breast Cancer Metastasis And Recurrence

A New study published in the Journal of Clinical Investigation suggests that administration of currently available drugs can stop the spread of breast cancer to other parts of the body. The study conducted by research teams at University of California San Diego School of Medicine and Moores Cancer Center report that the drugs target stem-like tumor cells that play a key role in cancer metastasis.

Stem-like tumor cells

Stem-like tumor cells play their role during the spread of cancer, before metastasis. They are responsible for cancer progression and recurrence as these are those cells that remain and grow in the body despite even after cancer treatments such as chemotherapy and radiation. The new study suggests that co-expression of cell surface receptor integrin αvβ3 and transcription factor Slug identifies these rare cells in patient-derived tumor samples. Moreover, this co-expression is observed in nearly 20% of the primary breast cancer cases.

Study Overview

Tumor samples were collected from the Women’s Healthy Eating and Living clinical trial. The research team identified stem-like tumor cells by recognizing their characteristic low levels of p53 upregulated modulator of apoptosis (PUMA). “If we are going to make a difference in the number of people who die of breast cancer we need to stop metastasis and we think we have a way to do it,” said Jay S. Desgrosellier, PhD, senior author and assistant professor in the Department of Pathology at UC San Diego School of Medicine.

Suppression of the tumor suppressor protein involved PUMA expression is crucial for tumor progression and the αvβ3/Src/Slug signaling pathway is the means by which this is achieved. However, the study found PUMA levels can be increased by either genetically disrupting this pathway, or by using the FDA-approved Src kinase inhibitor dasatinib In mice experiments, the overexpression of PUMA decreased tumor progression and metastasis by five times. The study also reports that increase in PUMA levels only target stem-like tumor cells that are beginning to spread and have no effect on the cells of the primary tumor cells.

"We are introducing a potential new therapeutic approach that is particularly useful in preventing new metastatic disease from forming," said Desgrosellier. "The inhibitors should be given when cancer cells have not metastasized or during early metastasis, when cells are still circulating. Disseminated cells are more sensitive to PUMA expression because they are already stressed. The cells in primary tumors are already established and are not affected by the inhibitors."

Reference:

1. Qi Sun, Jacqueline Lesperance, Hiromi Wettersten, Elaine Luterstein, Yoko S. DeRose, Alana Welm, David A. Cheresh, Jay S. Desgrosellier. Proapoptotic PUMA targets stem-like breast cancer cells to suppress metastasis. Journal of Clinical Investigation, 2017; DOI: 10.1172/JCI93707

Source-Medindia