Cancer Stem Cells Sensitivity Assay (STELLA) in Patients with Advanced Lung and Colorectal Cancer: A Feasibility Study

PLoS One. 2015 May 8;10(5):e0125037. doi: 10.1371/journal.pone.0125037. eCollection 2015.

Abstract

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.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / pharmacology*
  • Cell Separation / methods*
  • Colorectal Neoplasms / pathology
  • Drug Combinations
  • Drug Screening Assays, Antitumor / methods*
  • Feasibility Studies
  • Female
  • Humans
  • Liver Neoplasms / pathology
  • Lung Neoplasms / pathology
  • Lymphatic Metastasis / pathology
  • Male
  • Middle Aged
  • Neoplastic Stem Cells / drug effects*
  • Neoplastic Stem Cells / pathology
  • Pleural Effusion / pathology
  • Time Factors

Substances

  • Antineoplastic Agents
  • Drug Combinations

Associated data

  • ClinicalTrials.gov/NCT01483001

Grants and funding

This study was partially supported by Italian Association for Cancer Research (AIRC 5x1000) to MatildeTodaro, Giorgio Stassi and Federico Cappuzzo, by the Fondazione Ricerca Traslazionale (ForRT) to Federico Cappuzzo and by Istituto Toscano Tumori to Federico Cappuzzo and Armida D’Incecco. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.