Targeted Antiglycolytic Therapy Promising in Breast Cancer

Lara C. Pullen, PhD

July 08, 2011

July 8, 2011 (Chicago, Illinois) — The combination of 2 innovative strategies — metabolic therapy and imaging guidance — is more effective than the current treatments of surgical resection or tumor removal in the treatment of breast cancer.

Jeff H. Geschwind, MD, FSIR, professor of radiology, surgery, and oncology and director of vascular and interventional radiology at Johns Hopkins University School of Medicine in Baltimore, Maryland, presented the results of a study here at the Society of Interventional Radiology 36th Annual Scientific Meeting. The novel treatment strategy exploits tumor metabolism and leverages the interventional radiology's vast experience in minimally invasive treatment strategies.

Dr. Geschwind and colleagues used a minimally invasive ultrasound-guided intratumoral treatment strategy to deliver the antiglycolytic agent 3-bromopyruvate (3-BrPA) directly to breast tumors in mice. The strategy maximized 3-BrPA delivery to the tumor and minimized the exposure of healthy tissue to the 3-BrPA. The result was a statistically significant difference in tumor volume between treated and control mice. In the group treated with 5 mmol/L 3-BrPA, results were seen on day 6 of treatment (256 vs 1809 mm3 in the control group; P < .05); in the group treated with 1.75 mmol/L 3-BrPA, results were seen on day 12 (1160 vs 4188 mm3; P < .05).

Dr. Geschwind also presented data describing the research team's work to determine the half maximal inhibitory concentration of the breast cancer cell line used in the study (200 µmol/L). They characterized an in vitro dose-dependent decrease in adenosine triphosphate levels, starting at a concentration of 50 µmol/L of 3-BrPA. When tested using a wound-migration assay, the penetration of breast cancer cells treated with 100 µmol/L of 3-BrPA decreased by 70%, compared with untreated control cells.

One in 8 women is diagnosed with breast cancer during her life, and breast cancer is the second leading cause of cancer death in women in the United States. Increased cancer awareness and the implementation of screening programs have resulted in an increased proportion of early-stage carcinomas at the time of diagnosis. Unfortunately, a significant number of patients experience treatment failure after an initial response to chemotherapy or radiation.

Most cancer cells exhibit upregulation of the energy-producing glycolytic pathway. Dr. Geschwind explained to Medscape Medical News that "cancer cells have a unique way of finding enough glucose to satisfy their needs. There is a big dichotomy between normal cells and cancer cells and their needs for glucose. This is something that can be targeted."

The goal of therapy is to treat the process of cancer growth and to freeze the process of cancer metastases with 2 to 4 injections. It appears to do this by decreasing the expression and activity of matrix metalloproteinases (MMP)-2 and MMP-9, which are required for the migration and invasion of tumor cells.

Reed A. Omary, MD, MS, professor of radiology and biomedical engineering and vice chair of research in the Department of Radiology at Northwestern University in Chicago, Illinois, discussed the research with Medscape Medical News. "If this therapy can be successfully translated to patients, it could have a significant impact, as breast cancer affects so many women. Treatment options for breast cancer continue to evolve. While interventional radiologists have used imaging guidance to treat tumors elsewhere in the body (most commonly in the liver), Dr. Geschwind's innovative research expands this concept of local therapy to breast cancer."

When administered systematically, 3-BrPA therapy causes adverse effects. As targeted therapy, it appears to result in few adverse effects.

Although the research by Dr. Geschwind's team has thus far been performed primarily in animals, the protocol has been used to treat a couple of patients in Israel on a compassionate-use basis. The results were promising. Dr. Geschwind notes: "We have made a lot of progress, but we have to make an Investigational New Drug Application." He anticipates that this application will target liver cancer.

Dr. Geschwind reports serving as a consultant to Biosphere Medical, Biocompatibles, Bayer HealthCare, Guerbet, and MDS Nordion. Dr. Omary has disclosed no relevant financial relationships.

Society of Interventional Radiology (SIR) 36th Annual Scientific Meeting: Abstract 8. Presented March 29, 2011.

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