Dasatinib (BMS-35482) potentiates the activity of gemcitabine and docetaxel in uterine leiomyosarcoma cell lines.

A major ongoing challenge in cancer therapy is development of selective chemotherapeutics that can eradicate tumors with little or no side effects to the patient. Most of our current arsenal of anti-cancer drugs was developed to simply target replicating cells. Thus, while these drugs do kill tumor cells, they are also toxic to normal replicating cells in the body, such as those found in the bone marrow and in the lining of the intestines. Recent advances in tumor biology indicate that the environment surrounding tumor versus normal cells is different and can be exploited to improve anti-cancer drug selectivity. Specifically, solid tumors have a defect in metabolism of glucose that leads to the secretion of lactic acid. This forms an acidic microenvironment and accompanying pH gradient in tumor cells that is not present in normal cells. Our laboratory, in collaboration with investigators at Duke, Research Triangle Institute International, the National Cancer Institute, and DEKK-TEC, Inc. are developing analogs of the plant toxin, camptothecin, that are selectively active at acidic pH. To date, we have identified six such compounds, one of which is highly fluorescent and can be quantified by external biosensors to permit study of tumor pharmacokinetics and pharmcodynamics in situ in real time. This agent has remarkable activity in a pre-clinical model of pancreatic cancer and is currently being advanced to IND status for subsequent biomarker-based clinical evaluation. In addition to solid tumors, we collaborate with clinical oncologists in the Duke Division of Cell Therapy on translational research in leukemia and lymphoma. In particular, we are interested in optimizing combination chemotherapy regimens for established and novel drugs in stem/progenitor models of acute myelogenous leukemia. The overall objective is to move drug discovery and development toward more clinically relevant models that can help bridge the "valley of death" - barriers that currently limit translation of laboratory advances into clinical utility for cancer patients.

Dr. Andrew Nixon is Professor of Medicine in the Department of Medicine/Division of Medical Oncology at Duke University. He holds a BS in chemistry from Miami University, a PhD in biochemistry from Wake Forest University, and an MBA with a focus on healthcare management from Duke University/Fuqua School of Business. He is a nationally recognized expert in the development of cancer biomarkers and correlative science, with extensive experience leading large multi-center biomarker analyses. Dr. Nixon serves in various leadership roles within the National Cancer Institute (NCI), working with diverse multi-disciplinary teams focused on improving cancer patient outcomes through biomarker science. He serves as the national co-chair for the NCI Core Correlative Sciences Committee which adjudicates the use of biospecimens collected throughout the NCI National Clinical Trial Network (NCTN). Within the NCI-NCTN Alliance cooperative group, Dr. Nixon has multiple leadership positions including serving on the Alliance Board of Directors, co-chair of the Immuno-Oncology Committee, co-chair for Gastrointestinal Correlative Research, and has been an executive member of the Translational Research Program since its inception. Additionally, within the NCI-NCTN NRG cooperative group, he serves as a member of the Gynecologic Translational Science Committee and on the Gynecological Oncology Group - Partners Investigator Council Translational Research Subcommittee. Dr. Nixon is an American Society for Clinical Oncology (ASCO) Ambassador and has chaired various committees and led scientific and educational sessions at national conferences. Recently, Dr. Nixon has focused his research on cellular senescence and biomarkers of aging and early carcinogenesis. He serves as Principal Investigator for a large multi-center NIH grant to develop high-resolution tissue maps and biomarkers of cellular senescence as a part of the Senescence Network (SenNet) Consortium.

My primary research interest has focused on on novel therapeutics, biomarkers and clinical trial development for ovarian and endometrial cancer. My fundamental goal is to develop a strong translational research program at Duke University in the Gynecologic Oncology Division, where knowledge we glean from our basic science research can be incorporated into our clinical trial program. Specifically, my focus is on biologic therapy and molecular biomarkers to direct therapy in patients with ovarian and endometrial cancers to determine if a strategy that incorporates both clinical and genomic information can improve clinical outcome, minimize unnecessary toxicity, and impact positively on quality of life.

In addition I am interested in robotic-assisted laparoscopic surgery for women with endometrial, ovarian and cervical cancers, as well as for benign gynecologic conditions.