Cancer Stem Cell Chemotherapeutics Assay for Prospective Treatment of Recurrent Glioblastoma and Progressive Anaplastic Glioma: A Single-Institution Case Series

Ranjan, Tulika; Howard, Candace M.; Yu, Alexander; Xu, Linda; Aziz, Khaled; Jho, David H.; Leonardo, Jodi; Hameed, Muhammad; Karlovits, Stephen; Wegner, Rodney E.; Fuhrer, Russell; Lirette, Seth T.; Denning, Krista L.; Valluri, Jagan; Claudio, Pier Paolo

doi:10.1016/j.tranon.2020.100755

Cited by 20 publications

(21 citation statements)

References 25 publications

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“…Details regarding the CSCs cytotoxicity assay (ChemoID) procedure have been described elsewhere [ [27] , [28] , [29] , [30] , [31] , [32] , [33] ]. In brief, primary cancer cell cultures were initiated from malignant cells present in the ascites or pleural aspirates.…”

Section: Methodsmentioning

confidence: 99%

“…In brief, primary cancer cell cultures were initiated from malignant cells present in the ascites or pleural aspirates. CSCs were enriched from the primary cancer cell cultures (bulk of tumor cells) as described previously [ [27] , [28] , [29] , [30] , [31] , [32] , [33] ] using a novel cell culture bioreactor with a membrane that allows for gas exchange. Cells were counted and a range of 1 × 10 6 –1 × 10 7 cells were cultured for 7–10 days.…”

Section: Methodsmentioning

confidence: 99%

“…The cells were challenged for a 1-h pulse with the panel of anticancer drugs ( Table 1 ). MTT assay was performed 48-h following chemotherapy treatment to assess cell survival as previously described [ 27 , 28 , 30 , [32] , [33] , [34] ]. Inhibition of bulk of tumor cells and CSCs survival was measured for each concentration (average counts in five replicates ± SE) of a given treatment (15–18 different treatments per patient).…”

Section: Methodsmentioning

confidence: 99%

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

Howard

Zgheib

Bush

et al. 2020

Translational Oncology

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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.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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

Howard

Zgheib

Bush

et al. 2020

Translational Oncology

Self Cite

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“…In this context, the recent development of microfluidic devices, bioreactors, and biomaterials, has driven researchers into a 3D cell culture-based multidisciplinary approach to detect, profile and even treat dormant cancer cells, spanning from fundamental biology to high-throughput screening (87)(88)(89)(90)(91). Indeed, cells cultured in a 3D model system more closely mimick the in vivo conditions and address most of the factors that can impact cancer dormancy, such as cell-to-cell and cell-to-ECM interactions, tissue architecture, proteomic and metabolomics profiles, and oxygen levels (92).…”

Section: In Vitro and Ex Vivo Models Of Cancer Dormancymentioning

confidence: 99%

Tuning Cancer Fate: Tumor Microenvironment's Role in Cancer Stem Cell Quiescence and Reawakening

et al. 2020

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Cancer cell dormancy is a common feature of human tumors and represents a major clinical barrier to the long-term efficacy of anticancer therapies. Dormant cancer cells, either in primary tumors or disseminated in secondary organs, may reawaken and relapse into a more aggressive disease. The mechanisms underpinning dormancy entry and exit strongly resemble those governing cancer cell stemness and include intrinsic and contextual cues. Cellular and molecular components of the tumor microenvironment persistently interact with cancer cells. This dialog is highly dynamic, as it evolves over time and space, strongly cooperates with intrinsic cell nets, and governs cancer cell features (like quiescence and stemness) and fate (survival and outgrowth). Therefore, there is a need for deeper insight into the biology of dormant cancer (stem) cells and the mechanisms regulating the equilibrium quiescence-versus-proliferation are vital in our pursuit of new therapeutic opportunities to prevent cancer from recurring. Here, we review and discuss microenvironmental regulations of cancer dormancy and its parallels with cancer stemness, and offer insights into the therapeutic strategies adopted to prevent a lethal recurrence, by either eradicating resident dormant cancer (stem) cells or maintaining them in a dormant state.

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“…Eventually, emphasizing the importance of estimating prospective therapy response in precision medicine is warranted. For instance, a better OS in recurrent glioblastoma patients than previous data was achieved by using a systemic assay which firstly stratifies the cell kill rate to find an efficient one among different drug combinations targeting both CSCs and non-CSC cells [ 215 ]. This frontier attempt provided an auspicious way for the future treatment of recurrent EC patients or those with poor estimated prognosis.…”

Section: Therapeutic Strategies Targeting Csc In Ecmentioning

confidence: 99%

Linking Cancer Stem Cell Plasticity to Therapeutic Resistance-Mechanism and Novel Therapeutic Strategies in Esophageal Cancer

Zhou

Fan

Liu

et al. 2020

Cells

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Esophageal cancer (EC) is an aggressive form of cancer, including squamous cell carcinoma (ESCC) and adenocarcinoma (EAC) as two predominant histological subtypes. Accumulating evidence supports the existence of cancer stem cells (CSCs) able to initiate and maintain EAC or ESCC. In this review, we aim to collect the current evidence on CSCs in esophageal cancer, including the biomarkers/characterization strategies of CSCs, heterogeneity of CSCs, and the key signaling pathways (Wnt/β-catenin, Notch, Hedgehog, YAP, JAK/STAT3) in modulating CSCs during esophageal cancer progression. Exploring the molecular mechanisms of therapy resistance in EC highlights DNA damage response (DDR), metabolic reprogramming, epithelial mesenchymal transition (EMT), and the role of the crosstalk of CSCs and their niche in the tumor progression. According to these molecular findings, potential therapeutic implications of targeting esophageal CSCs may provide novel strategies for the clinical management of esophageal cancer.

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Cancer Stem Cell Chemotherapeutics Assay for Prospective Treatment of Recurrent Glioblastoma and Progressive Anaplastic Glioma: A Single-Institution Case Series

Cited by 20 publications

References 25 publications

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

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

Tuning Cancer Fate: Tumor Microenvironment's Role in Cancer Stem Cell Quiescence and Reawakening

Linking Cancer Stem Cell Plasticity to Therapeutic Resistance-Mechanism and Novel Therapeutic Strategies in Esophageal Cancer

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