Detection of minimal residual disease in patients with cancer: A review oftechniques, clinical implications, and emerging therapeutic consequences

The issue of minimal residual disease (MRD) manifesting itself by the prese nce of undetected disseminated isolated tumor cells in both tissues and hem atopoietic autografts from patients with early-stage malignancies or from p atients in clinical complete remission has been discussed widely during the last decade. Based on the current understanding of the pathogenesis of mal ignancy, disseminated tumor cells persisting after conventional oncologic t reatment modalities or after reinfusion of contaminated autologous hematopo ietic cells constitute the source of subsequent recurrence of disease. Acco rdingly, much emphasis is placed on the detection and characterization of d isseminated isolated tumor cells in both basic and clinical research. This effort is aimed at a better understanding of the processes of metastasis an d tumor dormancy and, ultimately, the estimation of prognosis, molecular mo nitoring, and the design of new therapeutic agents in oncology. In our revi ew, we used computerized (MEDLINE, Embase) and manual searches to summarize laboratory and clinical data concerning MRD focusing on the issue of MRD i n solid malignancies. We give a detailed overview of the methods used for t he detection and molecular characterization of disseminated tumor cells and of the prevalence and prognostic significance of the detection of MRD in p atients and hematopoietic autografts. Finally, we discuss the emerging ther apeutic consequences of the detection of disseminated tumor cells, with spe cial emphasis on the therapeutic potential of antibodies. We conclude that the detection of MRD represents a hallmark for the diagnosis, monitoring, a nd treatment of malignant conditions in future clinical trials.