A tale of two tumor targets: topoisomerase I and tubulin. The Wall and Wani contribution to cancer chemotherapy

Abstract

The seminal discoveries of camptothecin and Taxol by Wall and Wani are discussed in a manner that demonstrates the influence that these two compounds has had on the further development of natural product, natural product-derived, and (some) synthetic entities as potential drug leads that interact either with tubulin or with topoisomerase I. The major categories of tubulin interactive agents in terms of inhibition and promotion of tubulin polymerization are briefly discussed. Likewise, a brief discussion of topoisomerase I inhibitors is presented. Lists of tubulin interactive agents and topoisomerase I inhibitors in preclinical and clinical development are given in Tables 2 and 3, respectively. This review is not meant to be exhaustive, but does illustrate the profound impact that these two plant-derived agents have had on cancer chemotherapy.