PLoS ONE · 2015 · 15 citations · 26 references
MedicineCell BiologyOncologyChemotherapyMetastasisStem Cell BiologyCancer ProgressionCancer Stem Cell BiologyCancer Stem CellsChemotherapy ResistanceMalignant NeoplasmsTumorigenicity AssessmentCancer Cell Culture ModelsCancer Stem Cell - Mediated ResistanceCancer Stem Cell IsolationCancer Stem Cell MarkersCancer Stem Cell ModelsLymph Node MetastasesTherapy FailureTherapy-resistant Cancer Stem Cells
BACKGROUND: Cancer stem cells represent a population of immature tumor cells found in most solid tumors. Their peculiar features make them ideal models for studying drug resistance and sensitivity. In this study, we investigated whether cancer stem cells isolation and in vitro sensitivity assay are feasible in a clinical setting. METHODS: Cancer stem cells were isolated from effusions or fresh cancer tissue of 23 patients who progressed after standard therapy failure. Specific culture conditions selected for immature tumor cells that express markers of stemness. These cells were exposed in vitro to chemotherapeutic and targeted agents. RESULTS: Cancer stem cells were extracted from liver metastases in 6 cases (25%), lung nodules in 2 (8%), lymph node metastases in 3 (12.5%) and pleural/peritoneal/pericardial effusion in 13 (54%). Cancer stem cells were successfully isolated in 15 patients (63%), including 14 with lung cancer (93.3%). A sensitivity assay was successfully performed in 7 patients (30.4%), with a median of 15 drugs/combinations tested (range 5-28) and a median time required for results of 51 days (range 37-95). CONCLUSION: The approach used for the STELLA trial allowed isolation of cancer stem cells in a consistent proportion of patients. The low percentage of cases completing the full procedure and the long median time for obtaining results highlights the need for a more efficient procedure. TRIAL REGISTRATION: ClinalTrials.gov NCT01483001.
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