Clinical relevance of cancer stem cell chemotherapeutic assay for recurrent ovarian cancer

Abstract

Introduction Disease recurrence and progression of ovarian cancer is common with the development of platinum-resistant or refractory disease. This is due in large part to the presence of chemo-resistant cancer stem cells (CSCs) that contribute to tumor propagation, maintenance, and treatment resistance. We developed a CSCs drug cytotoxicity assay (ChemoID) to identify the most effective chemotherapy treatment from a panel of FDA approved chemotherapies. Methods Ascites and pleural fluid samples were collected under physician order from 45 consecutive patients affected by 3rd-5th relapsed ovarian cancer. Test results from the assay were used to treat patients with the highest cell kill drugs, taking into consideration their health status and using dose reductions, as needed. A retrospective chart review of CT and PET scans was used to determine patients' outcomes for tumor response, time to recurrence, progression-free survival (PFS), and overall survival (OS). Results We observed that recurrent ovarian cancer patients treated with high-cell kill chemotherapy agents guided by the CSCs drug response assay had an improvement in the median PFS corresponding to 5.4 months (3rd relapse), 3.6 months (4th relapse), and 3.9 months (5th relapse) when compared to historical data. Additionally, we observed that ovarian cancer patients identified as non-responders by the CSC drug response assay had 30 times the hazard of death compared to those women that were identified as responders with respective median survivals of 6 months vs. 13 months. We also found that ChemoID treated patients on average had an incremental cost-effectiveness ratio (ICER) between -$18,421 and $7,241 per life-year saved (LYS). Conclusions This study demonstrated improved PFS and OS for recurrent ovarian cancer patients treated with assay-guided chemotherapies while decreasing the cost of treatment.

Immuno-Stimulating Activity of 1,25-Dihydroxyvitamin D in Blood Cells from Five Healthy People and in Blasts from Five Patients with Leukemias and Pre-Leukemic States

“…The InDels present only in patients were checked for its functional annotation and the InDels that have functional impact on the encoded proteins, were then taken to the analysis. The list of mutations characteristic for leukemias and pre-leukemic states [ 19 , 20 , 21 , 22 ] are presented in Table 1 , while the list of all InDels detected in the patients’ malignant cells is given in the Supplementary Table S1 . Moreover, the information about the fusion genes expressed in patients’ blasts was read out from RNAseq data and presented in Table 1 .…”

Cancer Stem Cell Assay for the Treatment of Platinum-Resistant Recurrent Ovarian Cancer

“…In a previous prospective clinical investigation, we observed that recurrent ovarian cancer patients treated with high-cell kill chemotherapy agents guided by the CSCs assay had an improvement in the median PFS corresponding to 5.4 months (3 rd relapse), 3.6 months (4 th relapse), and 3.9 months (5 th relapse) when compared to historical data [ 37 ]. Additionally, in our previous study we also observed that ovarian cancer patients identified as non-responders by the CSC drug response assay had 30 times the hazard of death compared to those women that were identified as responders with respective median survivals of 6 months vs. 13 months [ 37 ], which is in agreement with our current findings.…”

“…Recent clinical trials, many of which have been supported by the Gynecologic Oncology Group (GOG), have investigated chemotherapy drugs, regimens, and reductive surgery methods in search of effective strategies to prevent EOC recurrence [ 37 ]. The AURELIA, OCEANS, and GOG-0213 phase-3 randomized trials have evaluated the use of bevacizumab in combination with chemotherapy for recurrent platinum-resistant and –sensitive ovarian cancer [ 46 – 49 ] and discovered that the PFS of patients treated with bevacizumab/chemotherapy was significantly prolonged (6.8 months versus 3.4 months, p<0.001) compared to patients treated with chemotherapy alone [ 37 ]. The median overall survival of these patients was 16.6 months for the bevacizumab/chemotherapy combination vs. 13.3 months for chemotherapy alone; however, this was not statistically significant (p=0.174).…”

“…We developed, a clinical laboratory assay (ChemoID ® ) that tests both CSCs and bulk of tumor cells directly derived from fresh tumor biopsies to predict the most effective chemotherapy agents’ combination to treat individual cancers [ 28 , 32 – 37 ]. Targeting of CSCs is a new paradigm in personalized anticancer treatment [ 38 ].…”

Evaluation of the potential of ultrasound-mediated drug delivery for the treatment of ovarian cancer through preclinical studies

“…The clinical management of patients would be positively impacted by the successful eradication of CSCs ( 78 ). The clinical importance of CSC has been demonstrated by the shorter time to cancer progression and higher overall survival rates in patients with chemotherapy-sensitive CSCs than without them ( 79 ).…”