Individualizing chemotherapy for solid tumors--is there any alternative?

Abstract

The burgeoning understanding of the molecular basis of carcinogenesis and tumor drug resistance is matched by an appreciation of the complexity of individual tumors. This complexity underlies the heterogeneity of response to treatment and is a major barrier to improving the outcome of solid tumor chemotherapy. While individualization of chemotherapy is theoretically attractive, past attempts to provide such information have produced many papers and little progress. However, the disparate molecular make-up of tumors of the same clinicopathologic type suggests that there may be no alternative and recent progress suggests that individualization of cancer therapy could have considerable benefits. In this review, we consider the alternative methods which might be employed and the requirements which need to be met before they are introduced. It will be some time before molecular analysis can predict chemosensitivity, although this may prove feasible for more specific agents than those currently in use. However, newly developed cellular chemosensitivity assays such as the ATP-tumor chemosensitivity assay allied to selected molecular measurement may already have the potential to select optimal therapy for patients. We need to develop a diverse series of acceptable and biologically logical regimens for each of the common tumor types, all of which can be tested in vitro.