Zoltan Szallasi, MD
Senior Research Scientist, Informatics Program
Boston Children's Hospital
Assistant Professor of Pediatrics
Harvard Medical School
Targeting deficiencies in DNA repair that can be exploited to treat aggressive breast cancers.
The goal of targeted therapy is to kill cancer cells without harming healthy cells and thereby reduce the risk that the patient will experience side effects from the drug. Tumor cells that have defects in DNA repair, and are thus unable to fix DNA damage, are good targets for drugs that cause DNA damage. Triple-negative and BRCA-driven breast cancers typically harbor specific DNA repair defects that are targets for a class of drugs called PARP inhibitors and DNA-damaging platinum-based drugs. Dr. Szallasi aims to find new strategies to expand the use of PARP inhibitors and other DNA-damaging drugs to benefit more patients.
Dr. Szallasi has developed a tool to detect DNA repair deficiency in tumor biopsies. He and his team are also working on identifying patients whose breast cancer has become resistant to PARP inhibitors because of increased activity of another DNA repair enzyme called polymerase theta. Ultimately, Dr. Szallasi’s goal is to expand the use of these efficient treatments to a broader group of breast cancer patients.
Dr. Szallasi will continue his work on the therapeutic exploitation of DNA repair pathway deficiencies in breast cancer. In the upcoming year, he will explore the role of a DNA repair process called nucleotide excision repair (NER) in a subset of breast cancers to demonstrate that NER-deficient breast cancers are most effectively targeted by therapy that takes advantage of this specific DNA repair aberration. Dr. Szallasi will also continue his work investigating the role of polymerase theta in the development of resistance to PARP inhibitor treatment in BRCA1-deficient breast cancers
Dr. Szallasi received his Doctor of Medicine degree from the University of Medicine in Debrecen, Hungary, in 1988. He did postdoctoral research in molecular pharmacology of cancer at the National Cancer Institute. As a faculty member, first at the Uniformed Services University of Health Sciences and currently at Boston Children's Hospital and Harvard Medical School, he has become active in the high throughput analysis of breast cancer. He has published over 100 peer-reviewed articles, mainly on the molecular pharmacology and high throughput analysis of cancer.
Dr. Szallasi's group is interested in the application of high throughput measurements for cancer research. They implemented several methods that increased the reliability of microarray and next generation sequencing measurements. They are also interested in approaches that combine genomic scale measurements in a manner that describe essential cancer biology in a robust fashion. Dr. Szallasi is currently developing methods that determine and quantify specific DNA repair pathway aberrations in human tumor biopsies. This work led to a DNA aberration profile-based method that predicts response to platinum-based therapy with high accuracy, and which is currently in the final stages of comprehensive clinical validation.
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