Aging issues in invasion and metastasis. Fertile ground for investigation.

Abstract

Ovarian cancer is a disease of predominantly older women and one in which metastases occur early and extensively. The unusual pattern of local metastasis is fertile ground for laboratory and clinical investigation. Tools are now available with which to study the complex cascade of invasion and metastasis as it underlies invasive ovarian cancer. The metastatic cascade involves five repetitive steps: angiogenesis, adhesion to the vascular basement membrane, local proteolysis, migration into and out of the vasculature, and proliferation at the secondary sites. Both in vivo and in vitro models of ovarian cancer are available; however, there are no systems targeted to understanding age-related differences in ovarian cancer biology. Progress in investigation of the biology of ovarian cancer has led to new diagnostic and therapeutic leads, including the use of adhesion receptors, protease secretion, and stimulation of tumor cell migration as potential markers and the identification of a new anti-cancer agent, CAI (NSC609974). CAI inhibits signal transduction pathways important in the regulation and activation of metastasis and proliferation. A phase I study has begun accrual at the National Cancer Institute; the protocol will contain no upper age limit.