PHILADELPHIA (October 5, 2015) – Triple Negative Breast Cancer (TNBC) is a subtype of breast cancer where <1% of the cells express estrogen or progesterone receptors, in addition to non-amplification of HER2-neu. As a consequence, TNBC is amenable neither to hormonal nor to HER2-targeted therapies, with the only treatments available consisting of surgery, radiotherapy and chemotherapy. In addition, chemotherapy seems to spare cancer stem cells (CSC), which preserve within themselves all the instructions to produce new neoplasm formations, and as such are a main cause of disease progression, development of metastases and relapses after treatment. That's why an international team of researchers, including medical oncologist Lori J. Goldstein, MD, from Fox Chase Cancer Center, has been looking at reparixin, an investigational study drug that targets breast cancer stem cells.
Laboratory and animal studies have shown that reparixin reduces the presence of breast cancer stem cells and the spread of disease (Ginestier, 2010). Following up on those promising results, a Phase Ib study in patients with metastatic breast cancer was initiated and completed, providing further data on the combination with chemotherapy and determined the recommended phase II dose (Schott, 2014).
Goldstein is one of the principal investigators that have launched a randomized Phase II trial of the investigational drug in combination with paclitaxel to assess the efficacy and safety of the combination in patients with metastatic TNBC. Enrolled patients are given the chemotherapy drug paclitaxel (brand name Taxol) in conjunction with either reparixin or placebo.
Goldstein is the principal investigator of the trial at Fox Chase. The investigational drug was developed by the Milan-based Italian biopharmaceutical company Dompé Farmaceutici, which is funding the study.
Cancer stem cells (CSCs) are like “blank-slate” cells with the ability to grow into any of the multiple types of cells found in a tumor—including those that leave the primary tumor, travel through the body, and establish distant metastatic growths. They have been identified in many cancer types, including prostate, brain, colon, pancreas, and breast.
“Rationally designed studies targeting breast cancer stem cells are a promising strategy to improve the management of breast cancer,” said Dr. Lori J. Goldstein, breast cancer clinical research leader at Fox Chase Cancer Center.
A protein receptor called CXCR1—found on the surface of breast cancer stem cells—has been strongly associated with the spread of disease, including triple negative breast cancer. Preclinical laboratory studies provide evidence that reparixin may block CXCR1, and in the lab, reparixin applied to tumor cells caused them to undergo widespread cell death. In mice bearing breast cancer, reparixin slowed tumor growth and the spread of the disease (Ginestier, 2010).
“Preclinical research suggests that treatments aimed at eradicating CSCs directly may result in more durable responses to therapy,” says Dr. Marcello Allegretti, chief scientific officer of Dompé Farmaceutici.
“While trastuzumab has become the standard treatment for HER-2 positive breast cancer, Triple negative breast cancer remains a subtype of the disease that can be difficult to treat and is an area where standard targeted therapies are not yet available,” says Allegretti.