Harvard Medical School
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 their cancer treatment. 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 continued to develop and validate diagnostic tools to identify DNA repair deficiencies in tumors from patients with breast or ovarian cancer that may lead to better treatment options. He and his team have discovered specific gene mutation signatures that may be able to identify breast cancers that harbor a defect in a type of DNA repair called nucleotide excision (NER). This type of DNA repair deficiency makes tumors particularly sensitive to cisplatin chemotherapy, making this gene signature a potential marker for patients most likely to respond to this therapy. In the process of this work, Dr. Szallasi developed a tool that allows for more accurate mutational analysis of tumor samples. He is now validating this diagnostic approach to identify DNA repair deficiencies in a cohort of patients with triple-negative breast cancer (TNBC).
Next, Dr. Szallasi will analyze the genes in tumors of patients with ovarian cancer who were treated with a PARP inhibitor. He and his team will correlate deficiencies in the BRCA genes and DNA repair deficiency with the benefit of PARP inhibitor therapy to determine how to personalize treatments for these patients. In addition, Dr. Szallasi will analyze data from a phase II clinical trial that looked at pre-operative cisplatin versus paclitaxel in patients with TNBC. They will calculate a NER deficiency score for each patient sample and determine whether NER deficiency is a predictor of sensitivity to cisplatin but not paclitaxel.
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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