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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 continue to develop tools that could potentially identify all breast cancers that can be treated with a class of drugs called PARP inhibitors.
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 of identifying breast cancers with alterations in the DNA repair pathway—an advance that is crucial for determining which patients will benefit from PARP inhibitors, a class of drugs that has been successful in treating those whose tumors harbor these defects.
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 in breast tumors that will be helpful in identifying patients who may benefit from PARP inhibitor therapy. Results from ongoing work include the follow findings:
- Long-term treatment with PARP inhibitors is less toxic than standard treatment with chemotherapy in laboratory models
- Inactivation of the HR pathway, while associated with BRCA deficiency, can occur through other mechanisms
What’s next: Dr. Szallasi will continue his current line of research in 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.