Robert Bast, Jr., M.D.
University of Texas
M.D. Anderson Cancer Center

"ARHI, an Imprinted Putative Tumor Suppressor Gene Whose Expression is Lost in Ovarian and Breast Cancer"

Understanding the Genetic Changes Behind Ovarian Cancer

This year in the United States, 26,000 women will develop epithelial ovarian cancer. More than half of them will die. That's why scientists are seeking to learn how molecular changes contribute to the development of ovarian cancer. By providing a better understanding of the genetic changes that underlie the development of this deadly cancer, basic science research can help guide new strategies for prevention, early detection, and more effective therapy for ovarian cancer.

Project Director Expertise

Dr. Robert C. Bast, Jr., is Head of the Division of Medicine at The University of Texas M.D. Anderson Cancer Center in Houston. For the past 15 years, Dr. Bast's laboratory has used the techniques of cellular and molecular biology to study growth regulation in ovarian and breast cancers, and he has contributed to major discoveries about cancer. His group was the first to identify CA 125, the first clinically useful marker for monitoring epithelial ovarian cancer. Today, a blood test is available that can help differentiate benign pelvic masses from malignant ones, which is helping women and their physicians detect ovarian cancer earlier. Dr. Bast also has helped develop methods for detecting and eliminating breast cancer cells from human bone marrow.

NFCR Research Overview and Findings

During the last decade, Dr. Bast's laboratory has demonstrated that epithelial ovarian cancer is generally a clonal disease and has focused upon molecular changes that occur during malignant transformation. Dr. Bast is working to identify the full spectrum of tumor suppressor genes associated with different cancers. Products of these genes are though to exert negative regulation of critical signaling pathways in normal cells. Isolating these genes and the pathways that regulate their expression should deepen understanding of the unique biology of ovarian cancer. In addition, by identifying genes that are downregulated, Dr. Bast expects to discover targets for gene therapy.

Dr. Bast and his team have identified multiple genetic changes associated with the development of ovarian cancers. They have cloned ARHI, which is widely believed to be a suppressor gene that is expressed in normal ovarian and breast epithelial cells, but not in the majority of ovarian and breast cancers. Through fine mapping of individual chromosomes, Dr. Bast and his team have found approximately 2,000 genes that are differentially expressed in normal and malignant ovarian epithelial cancer cells and narrowed to 79 those that are consistently downregulated in ovarian cancers with a certain genetic mapping sequence. Dr. Bast also has been able to suppress the growth of ovarian cancer by microcell-mediated transfer of a chromosome, and he has found functional evidence of a gathering point for a novel suppressor gene.

Future Research Goals

The long-term goal for Dr. Bast is to understand the molecular events that contribute to the development of ovarian cancer. Several supposed suppressor genes have been identified whose function is lost in sporadic ovarian cancers, but a larger number remain to be discovered.

Impact on Cancer Prevention, Treatment, or Cure

By evaluating potential tumor suppressor genes for ovarian cancer, studying the expression of specific genes, and mapping genes that could be harnessed to inhibit tumor growth, Dr. Bast and his laboratory are bringing us closer to using gene therapy to prevent ovarian cancer … and at the very least, to detect this deadly cancer early, when it is most treatable.