Strategies in cancer therapeutics: Targeting enzymes involved in cell cycle regulation and cellular proliferation

Tumor development, growth, and progression depend on some combination of altered cell cycle regulation, excessive growth factor pathway activation, and decreased apoptosis. Understanding the complex molecular mechanisms that underlie these processes should therefore lead to the identification of potential targets for therapeutic intervention. The estrogen receptor and HER-2/neu were among the earliest targets investigated, ultimately leading to the widespread use of tamoxifen and trastuzumab, respectively, in the treatment of breast cancer. Major research advances have since led to other classes of targeted therapies, including cyclin-dependent kinase inhibitors, historic deactylase inhibitors, and receptor tyrosine kinase inhibitors. The following review provides a discussion of the molecular biology associated with each of these types of therapies as well as a detailed summary of the preclinical and clinical data published on selected compounds from each of these subgroups.