Direct Cloning of Human Ovarian Cancer in Soft Agar: Clinical Limitations and Pharmacologic Applications

Abstract

Epithelial ovarian cancer is a disease which is well suited to the evaluation of in vitro tests for the individual selection of a patient’s chemotherapy, since a variety of antineoplastic drugs have significant activity in this disease (Young 1975). A predictive in vitro test could therefore potentially identify those drugs active for a particular patient and thereby spare her the unnecessary toxic effects of inactive drugs. In addition, many patients with advanced ovarian cancer have malignant effusions (ascites or pleural fluid) which provide an easily accessible source of cells for in vitro analysis. Additional malignant cells can also be obtained frequently by peritoneal lavage from patients who do not have clinically evident ascites (Ozols et al. 1981). The observation (Hamburger et al. 1978) that human ovarian cancer cells can form tumor colonies in soft agar along with the promising preliminary results of in vitro/in vivo correlations of drug resistance using this assay (Salmon et al. 1978; Alberts et al. 1980) led to our study on the growth of ovarian cancer tumor colonies from peritoneal washings as well as malignant effusions (Ozols et al. 1980a). In addition to evaluating the assays’ potential for individualization of chemotherapy, we have also used the human tumor stem cell assay (HTSCA) to investigate patterns of drug resistance and cross-resistance in ovarian cancer. In this report we will summarize our results with 215 ovarian cancer specimens, which demonstrate that, while the HTSCA has major limitations for the individualization of chemotherapy, the patterns of drug resistance and cross-resistance have provided clinically relevant information for the design of novel therapeutic approaches in ovarian cancer, such as intraperitoneal chemotherapy and high-dose cisplatin.