ABSTRACT

Within the œeld of natural products, marine organisms represent a relatively untapped resource for novel compounds of medicinal interest. The systematic evaluation of biological constituents from marine organisms as potential drug candidates did not begin in earnest until the late 1960s, when the U.S. National Cancer Institute (NCI) initiated a massive screening program directed at the discovery of new anticancer drug leads.1,2 Over the next 30 years, evaluation of isolates from the marine shell-less mollusk Dolabella auricularia (Aplyidae family) has led to the discovery of an impressive number of novel compounds possessing antineoplastic activity. Among the number of substances characterized to date, dolastatins 10 (1) and 15 (2) and the synthetic compounds derived from them show the most promising antitumor activity and are currently in human clinical trials in the United States, Europe, and Japan. This chapter will provide highlights of this work and will review recent progress in the discovery and development of the dolastatins as potential cancer chemotherapeutic drugs, with particular emphasis on dolastatins 10 and 15.