Carlos L. Arteaga, MD

2007-2008 BCRF Project:
Most hormone-dependent breast cancers that initially respond to anti-estrogens, such as aromatase inhibitors, almost invariably become resistant to these hormonal therapies over time. Dr. Arteaga and colleagues have shown that high levels of the HER2 proto-oncogene result in resistance to the aromatase inhibitor letrozole, an approved and increasingly used therapy for hormone-dependent breast cancers.

With funding from BCRF, the researchers have developed a laboratory model that overexpresses aromatase in the mammary gland. These models develop mammary gland hyperplasia. The scientists will model novel treatment combinations of anti-estrogens with inhibitors of EGFR/HER2 that will later be translated to clinical trials. These approaches may increase the efficacy of current anti-estrogen therapies and delay the emergence of resistance to aromatase inhibitors.

Mid-year Progress Report:
With funding from BCRF, Dr. Arteaga and his team have recently shown that PTEN loss in breast cancer cell lines confers resistance to anti-estrogenic therapies, and that co-targeting of ER and PI3K-activating pathways effectively suppresses the growth of PTEN-deficient cells. To investigate mechanisms of acquired resistance to aromatase inhibitor therapy, they have grown several ER+, estrogen-dependent cell lines in the absence of estrogens until estrogen-independent cells emerged. In characterizing the mechanism of acquired hormone-independent growth, they found that the PI3K pathway was upregulated, and cells showed sensitivity to PI3K inhibitors, suggesting that targeting this pathway may prevent the growth of cancers which escape hormonal therapy.

Bio:
Carlos L. Arteaga obtained his MD degree with honors in 1980 at the University of Guayaquil in Guayaquil, Ecuador. He trained in Internal Medicine and Medical Oncology at Emory University (Atlanta, GA) and the University of Texas Health Sciences Center in San Antonio, TX, respectively. In 1988, he joined the faculty at Vanderbilt University where he is now Ingram Professor of Cancer Research, Professor of Medicine and Cancer Biology, and member of the Division of Hematology-Oncology. In addition, he is Director of the Breast Cancer Research Program and Breast Cancer SPORE of the NCI-designated Vanderbilt-Ingram Comprehensive Cancer Center. His funded research focuses on the role of growth factor receptors and oncogenes in the progression of breast tumor cells as well as the development of molecular therapeutics in breast cancer. He is certified by the American Board of Internal Medicine in Internal Medicine and in Medical Oncology and has over 120 peer-reviewed publications relevant to his research in the molecular and cell biology of mammary neoplasia.

In 1998 he was elected into the American Society of Clinical Investigation (ASCI) and serves as a member of the NIH Parent Committee for Review of Cancer Centers (2004-2008), the Board of Scientific Advisors of the National Cancer Institute (1999-2004), the Breast Cancer Core Committee of the Eastern Cooperative Oncology Group (ECOG), and the Board of Directors of the American Association for Cancer Research (AACR; 2004-2007). He co-chairs the Developmental Therapeutics Committee of ECOG and chairs the Special Conferences Committee of the AACR (2002-2005). He is the recipient of the 2003 AACR Richard and Hinda Rosenthal Foundation Award for innovative work leading to progress in clinical breast cancer. He chaired the 2001 AACR/NCI/EORTC Meeting in Molecular Targets and Cancer Therapeutics and the AACR Special Conference Advances in Breast Cancer Research in 2003. He is Associate Editor or member of the Editorial Board of the Journal of Mammary Gland Biology & Neoplasia, Clinical Cancer Research, Breast Cancer Research, Molecular Cancer Therapeutics, Journal of Clinical Oncology, Clinical Proteomics, and Cancer Biology & Therapy.