Editors' ChoiceCancer

Taking Cancer Cells Out of Circulation

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Science Translational Medicine  18 Jun 2014:
Vol. 6, Issue 241, pp. 241ec104
DOI: 10.1126/scitranslmed.3009593

Despite intensive study, small-cell lung cancer (SCLC) remains a dire diagnosis with few treatment options and limited prognosis. However, the science and treatment of SCLC has taken a big step forward with a clever application of circulating tumor cells (CTCs). Hodgkinson et al. demonstrate that CTCs isolated from the peripheral blood of patients with SCLC can recreate the characteristics of a patient’s primary tumor when grafted into a mouse model, including its response or resistance to standard chemotherapy.

The study began with the isolation of EpCAM+/Cytokeratin+ CTCs from a 10-ml sample of patient’s blood. Concentrated CTCs from six patients were implanted into mice, and impressively, four out of six implants resulted in palpable tumors. The xenografts had histological features of SCLC and patient-specific patterns of chromosomal gain and loss. Because multiple tumors could be implanted in a mouse, deep sequencing could be used to examine both the heterogeneous way in which mutations were acquired as the tumors grew and the similarity of this process to known SCLC biology. In one case, a xenograft even began to metastasize to other organs within the mouse. Most importantly, the CTC-derived xenografts mirrored the donor patient’s clinical prognosis and sensitivity to standard treatment with the drugs carboplatin and etoposide.

The use of CTCs from SCLC patients to create living tumor models in laboratory mice provides obvious opportunities for basic research. But although it is tempting to imagine this technique being used to personalize cancer treatments at a tumor-specific level, one particular statistic in the study drives home both the challenges and importance of the work ahead: The average time to observe a palpable tumor in a mouse was 4.4 months, and the average life span of the corresponding donor patient was only 5.6 months.

C. L. Hodgkinson et al., Tumorigenicity and genetic profiling of circulating tumor cells in small-cell lung cancer. Nat. Med., published online 1 June 2014 (10.1038/nm.3600). [PubMed]

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