Abstract
Background: Chemotherapy is a mainstay of tumor therapy, however, it is predominantly applied according to empirically developed recommendations derived from statistical relapse rates occurring years after the treatment in the adjuvant situation and from progression-free interval data in the metastatic situation, without any possibility of individually determining the efficacy in the adjuvant situation and with loss of time and quality of life in the metastatic situation if the drugs chosen are not effective. Here, we present a method to determine the efficiency of chemotherapeutic drugs using tumor cells circulating in blood as the part of the tumor actually available in the patient’s body for chemosensitivity testing. Methodology/Principal Findings: After only red blood cell lysis, omitting any enrichment (analogous to other blood cell enumeration methods, including rare CD34 cells), the white cells comprising the circulating epithelial tumor cells (CETC) are exposed to the drugs in question in different concentrations and for different periods of time. Staining with a fluorescence-labeled anti-epithelial antibody detects both vital and dying tumor cells, distinguishing vital from dying cells through membrane permeability and nuclear staining with propidium iodide. Increasing percentages of dying tumor cells are observed dependent on time and concentration. The sensitivity can vary during therapy and was correlated with decrease or increase in CETC and clinical outcome. Conclusions/Significance: Thus, we are able to show that chemosensitivity testing of circulating tumor cells provides real-time information about the sensitivity of the tumor present in the patient, even at different times during therapy, and correlates with treatment success.
Highlights
For patients diagnosed with a malignant tumor, cure is presumably only possible if the tumor is completely eradicated
Chemotherapy is a mainstay of tumor therapy, it is predominantly applied according to empirically developed recommendations derived from statistical relapse rates occurring years after the treatment in the adjuvant situation and from progression-free interval data in the metastatic situation, without any possibility of individually determining the efficacy in the adjuvant situation and with loss of time and quality of life in the metastatic situation if the drugs chosen are not effective
In the present report we provide evidence that in vitro chemosensitivity testing of circulating epithelial tumor cells (CETC) using propidium iodide uptake, which results in nuclear red fluorescence, allows assessment, before treatment, of whether the tumor cells will be sensitive to the intended drugs
Summary
For patients diagnosed with a malignant tumor, cure is presumably only possible if the tumor is completely eradicated. As the second pillar of tumor therapy, chemotherapy has evolved and is applied after surgery as adjuvant chemotherapy, e.g. in breast and ovarian cancer, to eliminate such early disseminated cells, when no detectable tumor is present. Such therapies have been shown to avert metastasis formation and save lives in breast cancer patients [2]. These therapies have been developed in clinical trials using the statistical improvement of relapse-free survival as a measure This cannot, predict for the individual patient whether the JCT. Conclusions/Significance: we are able to show that chemosensitivity testing of circulating tumor cells provides real-time information about the sensitivity of the tumor present in the patient, even at different times during therapy, and correlates with treatment success
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