Lajos Pusztai, MD, D.Phil

2012-2013 BCRF Projects:

1) Dr. Pusztai has used past BCRF funding for the development of targeted therapies for triple negative breast cancer. He identified over 600 genes that have unusually high level of expression triple negative breast cancer and discovered 21 different, potentially druggable genes whose inhibition leads to cell death in this aggressive disease subtype.

Mid-year Progress: Dr. Pusztai's laboratory is studying if different regions of a single cancer or different metastatic sites in the same patient contain genetically different cancer cells. They have completed the DNA sequencing experiments in matching breast cancer and metastatic sites for four patients and data analysis is underway. Dr. Pusztai's team is also collecting samples from different areas of the same breast cancer. Nineteen different cancers were sampled this way so far, and the investigators plan to perform the genetic analysis within the next six months. These studies will help scientists understand the genomic diversity of breast cancers and could help focusing on shared abnormalities that sustain cancer in all different metastatic sites and locations of the cancer. This team will also examine if the genomic diversity of cancer itself could be used as a marker of prognosis or response to therapy (i.e. tumors made up by a diverse group of genomically different cancer cells may be more aggressive than more homogenous cancers).

2) Co-Investigator: David Rimm, MD, PhD, Yale University School of Medicine, New Haven, CT

In 2012-2013, Dr. Pusztai will lead a new study in collaboration with Dr. David Rimm at Yale that utilizes new sequencing technologies to study if different regions of a single cancer or different metastatic sites in the same patient contain genetically different cancer cells. Drs. Pusztai and Rimm will analyze DNA from HER2 positive (HER2+) breast cancers that were obtained from biopsies from patients who participated in the international randomized clinical trial NeoALTTO. This clinical trial tested the anticancer activity of lapatinib (Tykerb®) and trastuzumab (Herceptin®) or the combination of both of these drugs as preoperative treatment given together with paclitaxel chemotherapy for early stage (Stage I-III) breast cancers. Biopsies of the cancer were taken before any therapy and also during the second week of therapy and at the time of the surgery to samples cancer that may have survived treatment. The purpose of this BCRF-funded research is to identify mutations in genes that could predict who will benefit from these drugs and to identify what mechanisms lead to resistance to these therapies.

Mid-year Progress: In the collaboration with Dr. Rimm, Dr. Pusztai's team is analyzing genomic material (DNA) from HER2-positive breast cancers that were obtained from cancer biopsies from patients who participated in the randomized clinical trial NeoALTTO. This clinical trial tested the anticancer activity of lapatinib and trastuzumab or the combination of both of these drugs as preoperative treatment given together with paclitaxel chemotherapy for early-stage (stage I-III) breast cancers. Biopsies of the cancer were taken before any therapy and also during the second week of therapy and at the time of the surgery to samples of cancer that may have survived treatment. Since the start of this project in October, DNA has been extracted from the clinical trial material by the investigators who conducted the clinical trial and Dr. Pusztai's team is currently awaiting DNA samples to be sent to Yale Cancer Center for genomic analysis.

The purpose of this research is to identify mutations in genes that could predict who will benefit from these drugs and to identify what mechanisms lead to resistance to these therapies.

Bio:
Dr Pusztai is Director of Breast Medical Oncology and Co-Director of the Cancer Genetics Research Program at Yale School of Medicine. Prior to joining Yale, he led the pharmacogenomic program in the Department of Breast Medical Oncology at University of Texas MD Anderson Cancer Center.

Dr. Pusztai received his medical degree from the Semmelweis University of Medicine in Budapest, and his D.Phil. from the University of Oxford in England. He is currently Professor of Medicine. He is a practicing medical oncologist and clinical researcher who published over 150 peer-reviewed articles on the biology and treatment of breast cancer.

His research focuses on the developing pharmacogenomic markers of response to therapy and identifying methods to select the optimal treatment for individual patients. His group has proposed new clinical trial designs for predictive marker evaluation, introduced new pathologic measurements of residual cancer after neoadjuvant chemotherapy, created web-based chemotherapy response prediction models based on routine clinical variables and proposed genomic markers of chemo- and endocrine-therapy sensitivity.

Dr Pusztai is principal investigator of several clinical trials investigating new drugs and potential response markers. His research is supported by grants from the National Cancer Institute, the US Department of Defense, the American Society of Clinical Oncology, The Breast Cancer Research Foundation, and philanthropic research grants.