Journal of Cancer Stem Cell Research

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Prospective Analysis of Cancer Stem Cell Drug Response Assay for Glioblastoma Patients

Journal of Cancer Stem Cell Research

Abstract

Background: Over the past 20 years even with the aggressive standard of care (SoC) Stupp treatment protocol the prognosis of
glioblastoma (GBM) has only minimally improved from 12 to 14 months. This is due in large part to the presence of chemo- and
radiation-resistant GBM cancer stem cells (CSCs) that contribute to tumor propagation, maintenance, and treatment resistance.
We are using ChemoID, a CLIA certified and CAP accredited drug response assay to identify the most effective chemotherapy
treatment against CSCs and bulk of tumor cells from of a panel of chemotherapies, offering great promise for individualized
cancer management. A prospective study was conducted evaluating the use of the ChemoID drug response assay in
glioblastoma patients.
Methods: Fresh tissue samples were collected for drug sensitivity testing from 61 glioblastoma patients enrolled in IRB approved
protocol. Patients were prospectively monitored for tumor response, time to recurrence, progression-free survival (PFS), and
overall survival (OS). Odds Ratio (OR) associations of 12-month recurrence, PFS, and OS outcomes were estimated for CSCs,
bulk tumor and combined assay responses to treatment; sensitivities/specificities, areas under the curve (AUC) were examined.
Results: The data suggests that ChemoID guided treatment significantly enhanced tumor response. For every 5%increase in cell
kill of CSCs by assay-guided chemotherapy, 12-month patient response (non-recurrence of cancer) increased 2.5-fold, OR¼2.3
(P ¼ 0.01). Bulk of tumor assay was found not statistically significant. Median recurrence time was 20 months for patients with a
positive (> 40% cell kill) CSCs test versus only 3 months with a negative CSCs test, whereas median recurrence time was 13
months versus 4 months for patients with a positive (>55%cell kill) bulk test versus negative. Similar favorable results for theCSC
test were observed for PFS and OS outcomes.
Conclusions: The ChemoID CSCs drug response assay has the potential to increase the accuracy of bulk tumor assays to help
guide individualized chemotherapy choices. Glioblastoma cancer recurrence may occur quickly if the CSC test has a low cell kill
rate, even if the bulk tumor test cell kill rate is high.

  • Candace M. Howard, Jagan Valluri, Tulika Ranjan, Alexander Yu, Khaled Aziz, David Jho, Terrence Julien, Jody Leonardo, Anthony Alberico, Antonio Cortese, Krista Denning, and Pier Paolo Claudio
  • Journal of Cancer Stem Cell Research 2019, 6:e1004 (January 05, 2019)
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  • DOI: 10.14343/JCSCR.2018.6e1004

Editors-In-Chief

Pranela Rameshwar, Ph.D.
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Mariusz Ratajczak, M.D., Ph.D. ...
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Justin Lathia, Ph.D.
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