Perspectives on Cancer Chemoprevention Research and Drug Development

Abstract

This chapter focuses on the nature of carcinogenesis and provides an overview of the progress in this field, and presents successful strategies in chemoprevention. Chemoprevention is the use of agents to slow the progression of, reverse, or inhibit carcinogenesis. Chemopreventive agents modulate cancer risk at the molecular, cellular, tissue, and clinical levels. The mechanisms of these agents are defined by activities seen at the molecular and cellular levels, while chemopreventive efficacy is evaluated at the tissue and clinical levels. The chapter discusses principles of molecular target-based chemopreventive drug discovery and early development of five prototypical agent classes that showed significant chemopreventive activity, and reviews the rationale for their development. The chapter discusses the specific classes to the generality of molecular target- and empirical-based screening assays useful for discovery and early development of candidate chemopreventive agents. The rationale and methods for the development of a sequential drug development program, built on the rational mechanism-based and empirical agent discovery approach, are summarized. This program identifies and evaluates intermediate biomarkers as surrogate end points for cancer incidence. The chapter reviews the need for, the progress of, and the promise of chemoprevention at major cancer targets and describes a strategy for effectively using surrogate end points in defining chemopreventive efficacy. The chapter concludes with a discussion of major issues and challenges of chemoprevention drug development, and the tremendous opportunity it promises for reduction of the human cancer problem.