Ribavirin: Hope For Metastatic Breast Cancer | Dr. Kathleen T ...

American Association for Cancer Research
Associate Director for Clinical Research, Lady Davis Institute
Director, Clinical Research Unit, Jewish General Hospital
Director, Developmental Therapeutics, McGill Department of Oncology
James McGill Professor, Departments of Medicine and Oncology
McGill University
Montreal, Quebec, Canada

2010-2011 BCRF Project:
An important goal in breast cancer research is to develop less toxic and more effective personalized therapies, based on the clinical and molecular characteristics of the tumor. Two proteins (?targets?) are routinely tested in the assessment of breast cancer: the estrogen receptor (predicting response to endocrine therapies) and HER2 (predicting response to Herceptin?). Dr. Miller?s team will study a new target, eIF4E. eIF4E is found at high levels in about 50% of all breast cancers, and these tumors are more aggressive and more resistant to chemotherapy. Therefore, blocking the effects of eIF4E has been proposed as a possible new therapy for advanced breast cancer. Ribavirin, a non-toxic anti-viral drug, inhibits the activity of eIF4E and slows the growth of cancer cells with high levels of eIF4E in the laboratory. A recent clinical trial in leukemia performed by Dr. Miller and collaborators showed that ribavirin can effectively target eIF4E in patients and trigger remission of the cancer. It is important to test if ribavirin will have a similar anti-tumor effect in breast cancer.Dr. Miller and his team will conduct a clinical trial to study the effects of ribavirin in metastatic breast cancer patients who have high levels of eIF4E. To show a link between inhibition of eIF4E and anti-tumor effects, tumor samples will be taken before and after treatment to allow for analysis of eIF4E and other tumor markers. The group will also use breast cancer cells grown in the laboratory to identify possible drug combinations that could improve the effectiveness of ribavirin. They will test the combination of ribavirin with drugs commonly used to treat breast cancer, and will also screen a library of 5,000 drugs to find new combinations that could be tested in future clinical trials. This research will help the design of novel therapeutic strategies for a group of patients with poor-prognosis, metastatic breast cancer. eIF4E may be an important drug target in this group and detection of high levels of eIF4E in tumors could potentially be used as a guide to clinical decision making, as is currently the case for the detection of ER or HER2. Thus, while ER-positive patients receive tamoxifen and HER2-positive (HER2+) patients get Herceptin®, it is postulated that patients with high eIF4E could be treated with ribavirin. Importantly, ribavirin is easily accessible, commercially available, and no side effects were observed in the previous clinical trial in patients with leukemia. Better understanding the role of eIF4E in breast cancer may thus lead to better, personalized therapy.

Mid-year Progress:?An important goal in breast cancer research is to develop less toxic and more effective personalized therapies, which can be based on the presence or absence of certain proteins in the tumor. Two proteins (?targets?) are routinely tested in the assessment of breast cancer: the estrogen receptor (predicting response to endocrine therapies) and HER2 (predicting response to Herceptin?). Dr. Miller and colleagues are studying a new target protein, named eIF4E. eIF4E is present at high levels in about 50% of all breast cancers and these tumors are more aggressive and more resistant to chemotherapy. Ribavirin, a well-tolerated and widely used anti-viral drug, inhibits the activity of eIF4E and reduces growth of cancer cells in the laboratory. In a recent clinical trial of ribavirin in leukemia, the investigators observed dramatic responses. They now suggest that ribavirin may effectively target breast tumors that have high levels of eIF4E. The research team has initiated a clinical trial in metastatic breast cancer patients, which will give an indication of the action of ribavirin as a single agent and will guide the investigators in future experiments. Tumor samples from patients taking part in the clinical trial will be collected and analyzed to monitor the effect of ribavirin on eIF4E. In the meantime, Dr. Miller and colleagues are using breast cancer cells grown in the laboratory to better define how ribavirin blocks growth of these cells and to help us identify possible drug combinations that could improve ribavirin efficacy. This research will help guide the design of future clinical trials. This team?s overall goal is to help develop novel therapeutic strategies for the treatment of a major subgroup of patients with poor prognosis, metastatic breast cancer and to contribute to the design of better, personalized therapies.

Bio:
Dr. Wilson H Miller, Jr. is the James McGill Professor in the Departments of Oncology and Medicine, at McGill University, Montreal, Canada. He is Associate Director for Clinical Research of the Lady Davis Institute, and is Director of the Clinical Research Program in the Department of Oncology at McGill. Dr. Miller has a PhD from The Rockefeller University and an MD from Cornell University Medical College. He has held a faculty appointment in the Department of Medicine at Cornell and at the Memorial Sloan-Kettering Cancer Center in New York. Dr. Miller?s laboratory, at the Lady Davis Institute of McGill University, investigates molecular mechanisms underlying leukemia and breast cancer, with a focus on the development of novel targeted therapies. He has received a number of research awards throughout his career, including the Medical Research Council of Canada Scientist Award and the FRSQ Chercheur National Award. Dr. Miller is a well-known speaker at national and international meetings and sits on Peer Review Panels for the National Institutes of Health (US), the Canadian Institute of Health Research, the Ontario Cancer Research Network, and the Leukemia Lymphoma Society.

Dr. Miller?s laboratory uses several approaches to understand mechanisms of action and development of novel anti-cancer therapies. Current projects include the role of nuclear co-regulators of transcription and changes in chromatin in response and resistance to epigenetic therapies in acute promyelocytic leukemia and other hematopoietic malignancies. Another area of interest for the lab is the development of novel therapeutics for breast cancer, with a focus on new pathways regulating protein synthesis, modification and degradation.

Source: http://breastcancerbydrruddy.com/?p=3008

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