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Carlos L. Arteaga, MD
Professor of Medicine
Director Simmons Cancer Center
University of Texas, Southwestern Medical Center
Goal: To understand drug resistance and develop new approaches to improve clinical outcomes.
Impact: Dr. Arteaga is investigating why estrogen receptor (ER)-positive breast cancers become resistant to anti-estrogen (endocrine) therapies. His findings may lead to new or combination therapies that can overcome the mechanisms of resistance.
What’s next: Having previously identified a gene called FGFR1 as a potential therapeutic target to prevent endocrine resistance, Dr. Arteaga and his team are now conducting clinical trials with FGFR inhibitors in patients with breast cancers that have high levels of FGFR1.
Anti-estrogen drugs, such as tamoxifen or aromatase inhibitors, are effective treatments for patients with estrogen-driven breast cancers. However, many of these cancers will become resistant to these drugs, which presents a significant clinical challenge. Dr. Arteaga is exploring mechanisms of anti-estrogen resistance in order to devise more effective therapeutic approaches for patients who are less likely to respond to anti-estrogen therapy.
Full Research Summary
Research area: Understanding why estrogen receptor (ER)-positive tumors become resistant to therapy and developing new approaches to treatment that would improve clinical outcomes.
Impact: Estrogen receptor (ER)-positive breast cancers depend on female hormones and respond to anti-estrogen (endocrine) therapies, such as tamoxifen, aromatase inhibitors, and fulvestrant. However, many of these cancers eventually become resistant to such treatments and continue to grow. Dr. Arteaga is conducting studies to identify the mechanisms of resistance to these drugs, which he hopes will provide the basis for the development of new approaches to improve clinical outcomes in patients with ER-positive breast cancer.
Current investigation: He and his colleagues have been focused on FGFR1, a gene they have identified as a potential therapeutic target to prevent endocrine resistance. They are now conducting clinical trials with FGFR inhibitors in patients with FGFR1-amplified breast cancer.
What he’s learned so far: Dr. Arteaga has found that in tumors that are very hormone-dependent, treatment with the aromatase inhibitor letrozole potently inhibits tumor growth in ER-positive breast cancer. Conversely, tumors that harbor mechanisms of resistance continue to grow while on the drug. They have now completed laboratory studies that suggest amplification of FGFR1 causes resistance to both endocrine therapy and CDK4/6 inhibitors—the new standard of care for patients with ER-positive breast cancer.
What’s next: The team will continue to conduct clinical trials with FGFR inhibitors in patients with FGFR1-amplified breast cancer, the preliminary results of which show potential clinical activity of these drugs. They are now implementing studies to combine anti-estrogen drug letrozole with FGFR1 inhibitors and/or CDK4/6 inhibitors in patients with ER-positive tumors.
Dr. Arteaga is Professor of Medicine and Director of the Simmons Cancer Center at University of Texas, Southwestern Medical Center. He was formally Associate Director for Clinical Research, Director of the Breast Cancer Program, and Director of the Center for Cancer Targeted Therapies at the Vanderbilt-Ingram Cancer Center, where he also held the Donna S. Hall Chair in Breast Cancer Research and Professor of Medicine and Cancer Biology. Dr. Arteaga trained in Internal Medicine and Medical Oncology at Emory University and the UT Health Sciences Center San Antonio, respectively. He has over 250 publications in the areas of signaling by growth factor receptors and oncogenes, targeted therapies and biomarkers of drug resistance, and investigator-initiated clinical trials in breast cancer. Since 2002, he has directed the NCI-funded Vanderbilt Breast SPORE. He is a member of the ASCI and the Association of American Physicians. He received the AACR Richard & Hinda Rosenthal Award, a 2007-2017 ACS Clinical Research Professor Award, the 2009 Gianni Bonadonna Award from ASCO and the 2011 Brinker Award from the Susan G. Komen Foundation. He has served as AACR co-chair of the annual San Antonio Breast Cancer Symposium since 2009. He is Deputy Editor of Clinical Cancer Research and member of the Editorial Board of Cancer Cell and six other peer-reviewed journals. He is immediate past President of the AACR in 2015.
BCRF Investigator Since
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