Analysis of chemo-predictive assay for targeting cancer stem cells in 41 glioblastoma patients.

Abstract

Introduction: The prognosis of glioblastoma (GBM) treated with standard-of-care maximal surgical resection and concurrent adjuvant temozolomide (TMZ)/radiotherapy remains very poor (less than 15 months). GBMs have been found to contain a small population of cancer stem cells (CSCs) that contribute to tumor propagation, maintenance, and treatment resistance. The highly invasive nature of high-grade gliomas and their inherent resistance to therapy lead to very high rates of recurrence. For these reasons, not all patients with similar diagnoses respond to the same chemotherapy, schedule, or dose. Administration of ineffective anticancer therapy is not only costly but more importantly burdens the patient with unnecessary toxicity and selects for the development of resistant cancer cell clones. We have developed a drug response assay (ChemoID) that identifies the most effective chemotherapy against CSCs and bulk of tumor cells from of a panel of potential treatments, offering great promise for individualized cancer management. Providing the treating physician with drug response information on a panel of approved drugs will aid in personalized therapy selections of the most effective chemotherapy for individual patients, thereby improving outcomes. A prospective study was conducted evaluating the use of the ChemoID drug response assay in GBM patients treated with standard of care. Methods: Forty-one GBM patients (mean age 54 years, 59% male), all eligible for a surgical biopsy, were enrolled in an Institutional Review Board-approved protocol, and fresh tissue samples were collected for drug sensitivity testing. Patients were all treated with standard-of-care TMZ plus radiation with or without maximal surgery, depending on the status of the disease. 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 CSC, bulk tumor, and combined assay responses for the standard-of-care TMZ treatment; sensitivities/specificities, areas under the curve (AUCs), and risk reclassification www.transonc.com Tr a n s l a t i o n a l O n c o l o g y Volume 10 Number 2 April 2017 pp. 241-254

Efficacy of ChemoID® guided drug selection for palliative chemotherapy in advanced recurrent high-grade ovarian adenocarcinoma: Case study

“…Our recent clinical studies showed that patient derived CSCs from primary cancer cell cultures can be used in a drug response assay. 9,[30][31][32][33][34][35][36] We have optimized the enrichment of CSCs from tumor biopsies and have developed the ChemoID ® chemotherapy response assay, which measures the sensitivity of CSCs and bulk of tumor cells to chemotherapy to determine the most effective combination of anticancer drugs for solid tumors. 9,[30][31][32][33][34][35][36] …”

“…Details regarding the assay procedure have been described elsewhere. 9,[30][31][32][33][34]36 In brief, primary cultures were initiated by spinning down the malignant cells present in the ascites aspirate and by culturing the cells to sub confluence in RPMI-1640 medium supplemented with 5% irradiated, heat inactivated, defined fetal bovine serum (Thermofisher/Hyclone), and 50 U of penicillin and 5 µg of streptomycin/mL of medium (Thermofisher/Mediatech). Proliferation of CSCs was obtained using a culture methodology previously described 9,31 in which culture media, oxygenation, rotational speed of the culture vessel, temperature and CO2 were kept consistently constant for seven days.…”