Lajos Pusztai, MD, D.Phil

2009-2010 BCRF Project:
New laboratory methods developed in the past few years made it possible to examine all genes that are expressed in a small piece of human breast cancer and also to assess whether the genes are normal or defective. Anti-estrogens such as tamoxifen and the anti-HER2 antibody trastuzumab represent the only two currently available highly effective therapies for breast cancer that are targeted at particular molecular subsets of this disease, estrogen receptor-positive and HER-2-positive cancers respectively.

Dr. Pusztai's goal is to discover the next generation of drugs that are targeted to specific genomic abnormalities in human breast cancer. He and his team have performed detailed gene copy number analysis of 103 early stage breast cancers and identified frequently amplified or deleted genes. On average, 76 different chromosomal abnormalities were detected in single tumors. This indicates that every breast cancer harbors a large number of molecular abnormalities and there is great individual variability between cancers. Next they will test in the laboratory that some of the genes that show increased copy numbers may play an important biological role in the survival of these cancers. Among the most frequently altered (i.e. amplified) genes is fibroblast growth factor receptor 1 (FGFR1). In the current, second phase of this project the researchers will investigate the biological role of FGFR1 in breast cancer using experimental models in the laboratory.

In a separate project, funded through an ASCO Advanced Clinical Research Award, Dr. Pusztai is leading a prospective clinical trial, to find out if any one of three different molecular response predictors can identify a group of patients with metastatic breast cancer who have an at least a 25% chance to clinically benefit from the drug dasatinib. Clinical benefit is defined as either no change or decrease in the size of the cancer during treatment. The three different predictors that will be tested in this study are each based the expression of a relatively large number of genes. Dr. Pusztai and his tema have defined the three predictors and submitted these results for publication in January 2009, so that these become available for the larger scientific community for study. They have also secured all the necessary institutional and FDA approvals to start the clinical trial that will employ these tests to select patients for dasatinib therapy, and have also obtained further funding to conduct the trial. The trial was opened in June 2009.

Bio:
Dr. Pusztai leads the pharmacogenomic program in the Department of Breast Medical Oncology at MD Anderson Cancer Center. He received his MD degree from the Semmelweis University of Medicine in Budapest his DPhil from the University of Oxford in England. He is a practicing medical oncologist and clinical researcher and is an Associate Professor of Medicine. He has published over 130 peer-reviewed articles on the biology and treatment of breast cancer and contributed chapters to numerous books. Dr Pusztai's research focuses on the developing pharmacogenomic markers of response to therapy and identifying methods to select the optimal treatment for individual patients. His group also discovered a new mechanism of resistance to taxanes mediated by the microtubule binding protein Tau and developed the first multi-gene predictors of response to complex chemotherapy regimens. Dr Pusztai is principal investigator of several clinical trials investigating new drugs and his research is supported by grants from the National Cancer Institute, the US Department of Defense, The Breast Cancer Research Foundation and philanthropic research grants.

He has received several international awards including the Soros Scholarship by the George Soros Fundation, New York, the Overseas Research Students Award of the Vice-chancellors and Principals of the Universities of the United Kingdom, a Career Development Award from the US Department of Defense Breast Cancer Research Program and the MD Anderson Aventis Drug Development Award. He has published over 60 peer-reviewed articles on the biology and treatment of breast cancer. He is senior editor of a book on cell proliferation and cancer and also contributed chapters to books such as the Oxford Textbook of Pathology, Computational and Statistical Approaches to Genomics, Molecular Oncology of Breast Cancer, Molecular Pathology in Clinical Practice and the Textbook of Breast Cancer.