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Zoltan Szallasi, MD
Senior Research Scientist, Informatics Program
Boston Children's Hospital
Assistant Professor of Pediatrics
Harvard Medical School
Goal: To identify deficiencies in DNA repair that can be precisely targeted in aggressive breast cancers.
Impact: Dr. Szallasi aims to discover defects in DNA repair pathways—found in triple-negative and all BRCA-driven breast cancers—that can be precisely targeted therapeutically. His discoveries could lead to new, more effective treatments for breast cancer and advance precision medicine.
What’s next: He and his colleagues will focus on another DNA repair pathway that is a promising target for a subset of breast cancer patients.
Defects in DNA repair pathways are an underlying cause of the development and progression of breast cancer, and these defects often determine how a patient will respond to particular therapies. Dr. Szallasi is developing methods to identify breast cancers with alterations in DNA repair pathways. These advances are crucial to determine which patients will benefit from drugs that can treat tumors harboring DNA repair defects, such as PARP inhibitors, as well as to develop new drugs that target cancer cells with other DNA repair pathway deficiencies.
Full Research Summary
Research area: Identifying new targets for precision medicine in breast cancer.
Impact: 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’s BCRF research is focused on strategies to expand the use of PARP inhibitors and other DNA-damaging drugs to benefit more patients.
Current investigation: His work has focused on the diagnosis and treatment of patients with a type of DNA damage deficiency called homologous recombination deficiency (HRD). In the coming year his team will extend their studies to include another DNA repair deficiency called nucleotide excision repair deficiency (NERD), and possible therapeutic approaches for patients with breast cancers that harbor these defects.
What he’s learned so far: Dr. Szallasi has developed robust bioinformatics tools to measure HRD and NERD in breast tumors that will be helpful in identifying patients who may benefit from therapies that inhibit DNA repair pathways . In the past year, his team has further developed and validated predictive mutational signatures of various DNA repair pathway abnormalities in breast cancer.
What’s next: Dr. Szallasi will continue his research developing methods that determine and quantify specific DNA repair pathway aberrations in breast cancers to advance precision medicine to more patients.
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.