Carlos L. Arteaga, MD

2009-2010 BCRF Project:
Most hormone-dependent breast cancers that initially respond to anti-estrogenic therapies, 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. They demonstrated that loss of the PTEN tumor suppressor gene, a common mutation in cancer which activates the PI3K signaling pathway, confers resistance to anti-estrogenic therapies.

With funding from The Breast Cancer Research Foundation, the scientists have investigated mechanisms of acquired resistance to aromatase inhibitor therapy. They grew several ER+, estrogen-responsive cell lines in the absence of estrogens until estrogen-independent cells emerged. In characterizing mechanisms of acquired hormone-independent growth, they found that the PI3K pathway was upregulated, and cells showed sensitivity to PI3K inhibitors. Therefore, co-targeting both the PI3K and ER pathways may benefit patients with cancer that is resistant to hormonal therapy.

Mid-Year Progress Report:
Dr. Arteaga's laboratory has 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. The researchers demonstrated that loss of the PTEN tumor suppressor gene, a common mutation in cancer which activates the PI3K signaling pathway, confers resistance to anti-estrogenic therapies.

With BCRF funding, they have investigated mechanisms of acquired resistance to aromatase inhibitor therapy. They grew several ER+, estrogen-responsive cell lines in the absence of estrogens until estrogen-independent cells emerged. In characterizing mechanisms of acquired hormone-independent growth, they found that the PI3K pathway was upregulated, and cells showed sensitivity to PI3K inhibitors. Additionally, they have identified a requirement for ER in the hormone-independent growth of some ER+ breast cancer cell lines. Therefore, co-targeting both the PI3K and ER pathways may benefit patients with cancer that is resistant to hormonal therapy.

Bio:
Carlos L. Arteaga obtained his MD degree at the University of Guayaquil in Guayaquil, Ecuador. He trained in Internal Medicine and Medical Oncology at Emory University and the University of Texas Health Sciences Center in San Antonio, respectively. He joined the Vanderbilt faculty in 1989 where he holds the Donna S. Hall Chair in Breast Cancer Research and is Professor of Medicine and Cancer Biology in the Division of Hematology-Oncology. Arteaga serves as director of the Breast Cancer Program of the Vanderbilt-Ingram Cancer Center. He has over 200 publications in the areas of oncogene signaling 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.

In 1998 he was elected into the American Society of Clinical Investigation (ASCI) and in 2005 into the Association of American Physicians (AAP). He has served as member of the NCI SubCommittee A for Review of Cancer Centers, the Board of Scientific Advisors of the NCI, the Breast Cancer Core Committee of ECOG, and the Board of Directors of the AACR. He co-chaired the Developmental Therapeutics Committee of ECOG and chaired the Special Conferences Committee of the AACR. Arteaga is the recipient of the 2003 AACR Richard & Hinda Rosenthal Award, the 2007-2012 ACS Clinical Research Professorship Award and the 2009 Gianni Bonadonna Award from the ASCO. He is Deputy Editor of Clinical Cancer Research and Associate Editor or member of the Editorial Board of Cancer Cell, the Journal of Mammary Gland Biology & Neoplasia, Breast Cancer Research, Molecular Cancer Therapeutics, Journal of Clinical Oncology (past), Clinical Proteomics, and Cancer Biology & Therapy.