Clinical utility of circulating tumor cells: a role for monitoring response to therapy and drug development.

Detection of circulating tumor cells (CTCs) and circulating endothelial cells (CECs) have been described in a variety of solid tumors including breast, prostate, gastric, colorectal cancers and melanoma. Several studies have demonstrated that increased numbers of such CTCs are predictive of worse outcome in early-stage disease as well as decreased progression-free survival and overall survival in advanced stages. It is well known that malignancies comprise heterogeneous populations of cells. Therefore, CTCs and CECs may represent the most relevant tumor population - the tumor cell population most likely to metastasize. Recently, technical advances have rendered this population to be more easily accessible to both researchers and clinicians. As CTCs and CECs have become easier to repeatedly sample with a high degree of accuracy, these cells represent an attractive surrogate marker of the primary tumor. Studies have shown that CTCs and CECs can be phenotypically and genotypically compared with the primary tumor and are faithful representatives; and where phenotypic differences exist, such phenotypes can be exploited for selecting molecularly targeted therapies. Therefore, CTC and CEC enumeration and analysis represent a clinically meaningful tool for assessing prognosis, monitoring response to therapy, pharmacodynamic studies and rational selection of therapies in cancer patients.