A Novel Method for Monitoring Response to Chemotherapy Based on the Detection of Circulating Cancer Cells: A Case Report

Abstract

We describe a novel method for detecting micrometastasis in the blood stream of cancer patients based on RT-PCR amplification of tumor-associated carcinoembryonic antigen (CEA) mRNA. To increase sensitivity and specificity of RT-PCR, CEA transcript was selectively up-regulated in cancer cells by exposure of peripheral blood to non-toxic concentrations of staurosporine (ST). Thereafter, polyA(+) RNA was extracted from tumor cells captured by means of magnetic beads coated with a monoclonal antibody against a common human epithelial antigen. Finally, RNA was subjected to RT-PCR analysis of CEA transcript. Using this approach, we demonstrated an ST-mediated increase in CEA transcript in blood specimens collected from a patient with metastatic colon cancer before receiving treatment with 5-fluorouracil/leucovorin. After a few cycles of chemotherapy, CEA-positive tumor cells were no longer detected. Clinical follow-up of this patient indicated that treatment with chemotherapy induced a dramatic reduction in liver metastasis. Therefore, it can be hypothesized that lack of CEA transcript detection might be consistent with disappearance or at least marked reduction of circulating tumor cells.

Elevation in Peripheral Blood Circulating Tumor Cell Number Correlates with Macroscopic Progression in UICC Stage IV Colorectal Cancer Patients

“…Micrometastatic bone marrow tumor cells were successfully evaluated for the control of systemic therapy in breast cancer [18] as well as in recent colon cancer study [22]. A recent human breast cancer study showed that circulating tumor cells are significant independent prognostic factors [23].…”

Abscopal Effect and Drug-Induced Xenogenization: A Strategic Alliance in Cancer Treatment?

“…A number of in vitro experiments on human colorectal cancer cells demonstrated that this antimetabolite is able to substantially increase the expression of CEA epitopes on the tumor cell membrane in vitro [ 113 , 153 , 154 , 155 , 156 , 157 , 158 , 159 , 160 , 161 , 162 ]. This effect has been exploited to facilitate the detection of circulating colon cancer cells in patients [ 163 , 164 ]. In the case of melanoma cells, treatment in vitro with 5-FU sensitized cells to lysis induced by cytotoxic CD8+ T cells (CTL) recognizing the G209 antigen [ 165 ].…”

Disseminated and circulating tumor cells in gastrointestinal oncology

“…For chemotherapy management, some reports with limited patient numbers, have suggested that variations in CTC counts may be associated with treatment response [104]. For this application, the cytological CellSearch® technique has achieved very strong evidence, with several studies published on metastatic colorectal cancers ( Table 2).…”