An Algorithm for the Preclinical Screening of Anticancer Drugs Effective against Brain Tumors

Abstract

The anticancer drugs screening program is a long and expensive process. It is estimated that only 5% of drugs entering clinical trials are approved by the FDA. Moreover, many of the drugs that enter clinical trials are often of limited use in clinical practice, and most cancers remain untreatable. Brain tumors are particularly difficult to treat due to the presence of the blood brain barrier that limits the penetration of anticancer drugs. Additionally the isolation from most brain tumors of putative cancer stem cells and novel models of cancer stem cell biology suggest that anticancer drugs should be delivered for prolonged time and at higher concentrations to deplete any potential tumorigenic cell. In this paper, current concepts of cancer stem cell biology and novel concepts of anticancer drugs screening are integrated to develop a seven-steps algorithm as a guideline for the preclinical evaluation of active compounds for the treatment of brain tumors. The flexibility of the algorithm allows the inclusion of alternative studies to exhaustively investigate anticancer drugs and creates multiple opportunities where decisions to engage or not in early clinical trials can be made providing a useful tool for translational research in neurooncology.