David Rimm, MD, PhD

2012-2013 BCRF Project:
Co-Investigator: Lajos Pusztai, MD, D. Phil, Yale University School of Medicine

In 2012-2013, Dr. Rimm will lead a new study in collaboration with fellow BCRF grantee, Dr. Lajos Pusztai 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:
David Rimm, MD, PhD is a Professor in the Department of Pathology at the Yale University School of Medicine. He completed an MD-PhD at Johns Hopkins University Medical School followed by a Pathology Residency at Yale and a Cytopathology Fellowship at the Medical College of Virginia. Dr. Rimm is the Director of Yale Pathology Tissue Services and the Director of Translational Science in Pathology. His lab group (15 researchers) focuses on quantitative pathology using the AQUA® technology invented in his lab with projects related to predicting response to therapy in breast cancer and predicting recurrence or metastasis in melanoma and lung cancer. He also has a group working on primary cell culture, circulating tumor cells and in situ miRNA and mRNA analysis. He is currently supported by 11 grants from both public and private sources. He is an author of over 230 peer-reviewed papers and 8 patents and is the scientific co-founder of HistoRx, a digital pathology company and Metamark Genetics, a prognostic determinant company.