In vitro preclinical models for a rational design of chemotherapy combinations in human tumors

Today, drug combinations are frequently used in the treatment of cancer to increase therapeutic efficacy. Currently used clinical protocols for cancer combination therapies are mainly obtained empirically or on the basis of r esults from previous clinical trials. Information obtained from clinical pr otocols is invaluable, but it is time-consuming, expensive and does not pro vide data on the biochemical and molecular mechanisms of interaction of the drugs used in combination treatments at cellular level. Therefore, in vitr o drug combination studies on established cell lines or primary cell cultur es play an important role in designing and optimising combination protocols . A variety of in vitro assays and different mathematics models have been d eveloped to investigate cytotoxic effects and to analyse the type of drug i nteractions. Increased knowledge of the cellular targets of traditional and new drugs and the development of new technologies have resulted in a new r ole for the in vitro tests which are no longer used only to evaluate the cy totoxic effects of drugs, but also to investigate the interference on cell cycle, induction of apoptosis and molecular or biochemical interactions. A review on in vitro preclinical tests used to evaluate the effects of drug c ombinations and to design the rationale of combined chemotherapy protocols is presented. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.