In vitro evaluation of combination chemotherapy against human tumor cells (Review)

Combination therapy with multiple drugs or with multiple modalities is common practice in the treatment of cancer. The purpose of using drugs in combinations is to increase the therapeutic efficacy, decrease toxicity toward the host and minimize or delay the development of drug resistance. Presently used clinical protocols for cancer combination therapy are mainly obtained empirically or from clinical trials. Accumulation of experience from clinical trials is invaluable but is a slow and expensive process. Also, due to heterogeneous patient populations exposed to different environments, human clinical data frequently cannot be used for quantitative synergy determinations. Therefore, in vitro quantitative drug combination studies with cultured tumor cells are becoming imperative either as prospective studies or as adjuvant assessment for combination therapy. In recent years, a variety of in vitro assays have been developed to examine cytotoxicity or biochemical effects of drugs on cultured tumor cells. These methods can, not only quickly predict the potential therapeutic effects of the combined agents, but also provide the information or clues to the possible mechanisms of drug interactions. In addition, with the better understanding of various antineoplastic drugs and the development of new technologies to characterize actions of the drugs, the in vitro study of combination therapy is no longer limited to the measurement of cytotoxic effects. Instead, many other studies, such as cell cycle analyses, detection of apoptosis and biochemical analyses of drug interactions have also become common methods for the in vitro evaluation of combination drug therapy.