Preclinical Screening for New Anticancer Agents

Abstract

Cancer chemotherapy is a rather young discipline. It has been pursued with scientific vigor and multinational collaborations only since the mid-20th century. Although 92 approved anticancer drugs are available today for the treatment of more than 200 different tumor entities, effective therapies for most of these tumors are lacking (1). Out of the 92 registered drugs, 17 are considered by oncologists to be more broadly applicable and 12 additional agents are perceived as having certain advantages in some clinical settings (2). They are mostly cytotoxic in nature and act by a very limited number of molecular mechanisms. Thus, the need for novel drugs to treat malignant disease requiring systemic therapy is still pressing. Public institutions, the pharmaceutical industry, and, more recently, small business and biotech companies create hundreds of thousands of compounds with potential anticancer activity. Only a certain number of drugs and concepts, however, can be evaluated clinically because of cost and ethical considerations. A preselection, called the screening process, is therefore required. The aim of screening efforts is to identify products that will produce antitumor effects matching the activity criteria used to define which compounds can progress to the next stage in the preclinical development program. Anticancer drug screening can be performed using various types of in vitro and in vivo tumor models. The ideal screening system, however, should combine speed, simplicity, and low costs with optimal predictability of pharmacodynamic activity.