Carlos L. Arteaga, MD
Donna S. Hall Chair in Breast Cancer Research
American Cancer Society Clinical Research Professor
Professor of Medicine and Cancer Biology
Director, Breast Cancer Research Program Vanderbilt-Ingram Cancer Center (VICC)
Associate Director for Clinical Research at VICC
Vanderbilt University School of Medicine
2013-2014 BCRF Project:
(The Play for P.I.N.K. Award)
Most estrogen receptor-positive (ER+) breast cancers depend on female hormones and initially respond to anti-estrogen therapies, such as aromatase inhibitors (AIs) and fulvestrant (faslodex®). However, many of these cancers eventually become resistant to these therapies. Dr. Arteaga has found that ER+ breast cancer cells and tumors deprived of estrogen maintain estrogen-independent ER function. This suggests that a drug that induces degradation of ER, such as fulvestrant or a more potent ER downregulator (degrader) would be more effective than an AI or highly complementary with an AI in patients with ER+ breast cancer.
Dr. Arteaga’s team has shown that the oral ER downregulator ARN-673 is superior to fulvestrant against human breast tumors grown in laboratory models. This drug has entered a phase I clinical trial at Vanderbilt. The phosphatidylinositol-3 kinase (PI3K)/AKT signaling pathway is critical for the growth of breast cancers that adapt to anti-estrogen therapy. Major effectors downstream in the PI3K pathway are AKT and p70S6K, oncogenes that promote cell growth and survival. Data generated in Dr. Arteaga’s laboratory with BCRF support have shown that combined treatment with ARN-673 and the pan-PI3K inhibitor BKM120 induces regression of ER+ tumors that harbor an activating mutation in PIK3CA. Similarly, treatment with fulvestrant and the AKT/p70S6K inhibitor AZD5363 induces tumor regression. These data suggest that ER+/PI3K-mutant tumors would benefit from endocrine therapy in combination with PI3K/AKT pathway inhibitors. Although not yet approved by the FDA, ARN-673, BKM120 and AZD5363 are all in clinical development and these data provide a basis for their use in patients with ER+ breast cancer.
In more recent work, Dr. Arteaga discovered that a mutant Src family kinase (LYND189Y) can coexist with PIK3CA mutations in ER+ tumors resistant to estrogen deprivation. LYND189Y accelerates estrogen-independent growth and maintains PI3K activity in cells treated with a combination of fulvestrant and the pan-PI3K inhibitor BKM120. Further, the Src family kinase inhibitor dasatinib enhances the antitumor effect of BKM120 and fulvestrant in ER+/PI3K-mutant tumors. These results suggest LYN alterations mediate escape from anti-estrogens in a subset of ER+ breast cancers. Since some ER+ breast cancer cells maintain ER transcriptional activity despite estrogen deprivation, Dr. Arteaga’s team is now identifying kinase signaling pathways that promote estrogen-independent ER transcription and cell growth.
Carlos L. Arteaga obtained his M.D. 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. He joined the
Vanderbilt faculty in 1989 where he now holds the Donna S. Hall Chair in Breast Cancer Research and serves as Professor of Medicine and Cancer Biology in
the Division of Hematology-Oncology in the Department of Medicine. Arteaga is Associate Director for Clinical Research at the NCI-designated
Vanderbilt-Ingram Comprehensive Cancer Center (VICC) and directs the Breast Cancer Program of the VICC. He has over 250 publications in the areas of
signaling by growth factor receptors and oncogenes in breast tumor cells as well as the development of molecular therapeutics and biomarkers of drug action
in breast cancer. Arteaga directs the NCI-funded Vanderbilt Breast Cancer SPORE where he leads a number of investigator-initiated clinical trials. He is
funded by NCI, ACS, the DOD Breast Cancer Research Program, Stand Up 2 Cancer/AACR, and the Komen and Breast Cancer Research Foundations. 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 serves (or has served) as member of the NCI Parent Committee for
Review of Cancer Centers (Subcommittee A; 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-chaired the Developmental Therapeutics Committee of ECOG and chaired the Special Conferences Committee of the AACR (2002-2008). Arteaga is the
recipient of the 2003 AACR Richard & Hinda Rosenthal Award and more recently received the 2007-2012 ACS Clinical Research Professorship Award, the 2009
Gianni Bonadonna Award from the American Society of Clinical Oncology (ASCO), and the 2011 Brinker Award for Scientific Distinction from the Susan G. Komen
for the Cure Breast Cancer Foundation. He has chaired the AACR Special Conference Advances in Breast Cancer Research in 2003, 2005, 2007, and
2009. He is Deputy Editor of Clinical Cancer Research and Associate Editor or member of the Editorial Board of Cancer Cell, theJournal of Mammary Gland Biology & Neoplasia, Breast Cancer Research, Molecular Cancer Therapeutics, Journal of Clinical Oncology (past), Clinical Proteomics, and Cancer Biology & Therapy.