Ovarian cancer, Part I: Biology

The ovary is among the more complex organs of the body and its functions are achieved by numerous cell types. All of these cell types have some tendency to undergo malignant transformation, but the vast majority of ovarian cancers are believed to be the result of malignant transformation of the ovarian surface epithelium. The concept that most ovarian cancer arises from this modified peritoneal mesothelium is credited to Sir Spencer Wells in 1872. Ovarian cancer is the most frequently fatal gynecologic malignancy, and approximately 20,000 cases per year are diagnosed in the United States. Progress in understanding the biology of this disease, including factors involved in its etiology, progression, and tendency to change from a relatively chemotherapy-sensitive tumor to one with marked drug resistance, has been slow. In this review, the complex features of the normal ovarian surface epithelial cells are considered in relation to the etiology and progression of the disease. The hypothesis that incessant or repetitious ovulation contributes to the initiation of the disease is explored in detail based on experimental data, epidemiologic information, and the potential for antioncogene inactivation in this interesting cell type. Lastly, based on the experimental data available, potential mechanisms of resistance to platinum, the cornerstone of aggressive ovarian cancer therapy, are discussed, as are approaches to overcoming drug resistance. It is hoped that the reader will be left with the feeling that the pace of our understanding of the biology of ovarian cancer is increasing at such a rate that answers to the questions of etiology and why chemotherapy often fails will be known in the foreseeable future.