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David Cortez, PhD
Ingram Professor of Cancer Research
Professor of Biochemistry
Vanderbilt University School of Medicine
Goal: To identify new strategies that would improve outcomes for patients with triple negative breast cancer (TNBC).
Impact: Dr. Cortez is conducting studies to develop strategies to overcome resistance to a targeted therapy (olaparib) for BRCA-mutation associated cancers, which have a higher likelihood of also being triple negative (TNBC). His findings could expand the number of patients who may benefit from olaparib and improve outcomes for more patients with TNBC.
What’s next: He and his team will continue to investigate resistance mechanisms and, more generally, to understand how tumor cell defects in DNA repair provide opportunities for other therapies like olaparib.
In 2017, the first targeted therapy for BRCA mutation-associated cancers, olaparib (Lymparza®), was approved by the FDA. This was followed by approval of a second targeted therapy in the same class called talazoparib (Talzenna®). These drugs are in a class of drugs called PARP inhibitors. They work by targeting a protein called PARP. Cells with deficient DNA repair, like those with mutations in BRCA genes, rely on PARP as an alternative DNA repair method. Blocking PARP in these cells results in cell death. Unfortunately, as with most therapies, resistance can arise. Dr. Cortez is conducting studies to develop strategies to overcome resistance to olaparib so more patients can benefit from the therapy and other drugs like it.
Full Research Summary
Research area: Improving outcomes for patients with triple negative breast cancer (TNBC) caused by mutations in the BRCA1 gene.
Impact: BRCA1-driven breast cancers have a higher likelihood of also being triple negative and aggressive. The first targeted therapy for BRCA-driven cancers, olaparib, was approved in 2017 for the treatment of HER2-negative metastatic breast cancers that harbor mutations in BRCA1/2, most of which are triple negative. Unfortunately, as with most therapies, resistance can arise. Dr. Cortez is investigating the mechanisms of resistance to this promising new therapy in order to develop new strategies that will allow more patients to benefit from olaparib and other drugs like it.
Current investigation: In addition to their studies of resistance to olaparib, Dr Cortez is investigating how other DNA repair pathways provide new opportunities for targeted therapies.
What he’s learned so far: In the last year, Dr. Cortez uncovered a new DNA repair mechanism that could provide a new opportunity for targeted therapy in breast cancer with mutations in DNA repair genes.
What’s next: He and his team will continue their investigations into the mechanisms of resistance to PARP inhibitors and also investigate other proteins involved in DNA repair that could be new therapeutic targets. They plan to translate their findings into clinically useful information in collaboration with clinicians conducting ongoing clinical trials.
Dr. Cortez graduated summa cum laude from the University of Illinois at Champaign-Urbana with Highest Honors in Biology and Biochemistry. He received his doctorate in 1997 in Molecular Cancer Biology from Duke University. After postdoctoral training as a Jane Coffin Childs Fellow at the Baylor College of Medicine, Dr. Cortez joined the Vanderbilt faculty in 2002. He was promoted to Associate Professor in 2007 and Professor of Biochemistry and Ingram Professor of Cancer Research in 2009. Dr. Cortez is Director of Graduate Studies in the Department of Biochemistry, and a member of the Editorial Boards of the journals Cell Reports, Molecular and Cellular Biology, and Journal of Biochemistry. He became co-leader of the Genome Maintenance Program in the Vanderbilt-Ingram Cancer Center upon its inception in 2007.
Dr. Cortez’s research focuses on the mechanisms that maintain genome integrity. His research has been published in journals including Science, Genes and Development, Cell Reports, Molecular and Cellular Biology, Journal of Biological Chemistry, Proceedings of the National Academy of Sciences, Cancer Research, and Molecular Cell. He has received several awards recognizing his scientific achievements including the Howard Temin Award from the National Cancer Institute, the Wilson S. Stone Memorial Award, and a Pew Scholar Award from the Pew Charitable Trusts.