Promising survival for patients with glioblastoma multiforme treated with individualised chemotherapy based on in vitro drug sensitivity testing

Iwadate, Yasuo; Fujimoto, Shuichi; Namba, Hiroki; Yamaura, Akira

doi:10.1038/sj.bjc.6601376

Cited by 27 publications

(23 citation statements)

References 24 publications

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“…The dearth of effective drugs for treating glioma has limited assessment of the predictive value of in vitro sensitivity testing for this tumour type. Nevertheless, available evidence does argue that in vitro sensitivity testing can assist in selecting treatments for glioblastoma patients (Iwadate et al, 2003).…”

Section: Discussionmentioning

confidence: 99%

In vitro sensitivity testing of minimally passaged and uncultured gliomas with TRAIL and/or chemotherapy drugs

et al. 2008

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TRAIL/Apo-2L has shown promise as an anti-glioma drug, based on investigations of TRAIL sensitivity in established glioma cell lines, but it is not known how accurately TRAIL signalling pathways of glioma cells in vivo are reproduced in these cell lines in vitro. To replicate as closely as possible the in vivo behaviour of malignant glioma cells, 17 early passage glioma cell lines and 5 freshly resected gliomas were exposed to TRAIL-based agents and/or chemotherapeutic drugs. Normal human hepatocytes and astrocytes and established glioma cell lines were also tested. Cross-linked TRAIL, but not soluble TRAIL, killed both normal cell types and cells from three tumours. Cells from only one glioma were killed by soluble TRAIL, although only inefficiently. High concentrations of cisplatin were lethal to glioma cells, hepatocytes and astrocytes. Isolated combinations of TRAIL and chemotherapy drugs were more toxic to particular gliomas than normal cells, but no combination was generally selective for glioma cells. This study highlights the widespread resistance of glioma cells to TRAIL-based agents, but suggests that a minority of high-grade glioma patients may benefit from particular combinations of TRAIL and chemotherapy drugs. In vitro sensitivity assays may help identify effective drug combinations for individual glioma patients.

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Section: Discussionmentioning

confidence: 99%

In vitro sensitivity testing of minimally passaged and uncultured gliomas with TRAIL and/or chemotherapy drugs

et al. 2008

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“…The ex vivo responses to these agents are often nonselective and more diffi cult to interpret and translate to clinical patient care. Second, we focused on leukemias, whereas many previous studies have focused on solid tumors (28)(29)(30)(31)(32)(33), where representative samples are diffi cult to acquire and consecutive samples from recurrent disease are typically not available. Third, we measured selective anticancer effects as compared with normal bone marrow mononuclear cells, which makes it possible to identify cancer-selective drugs with potential for less systemic toxicity.…”

Section: Research Articlementioning

confidence: 99%

Individualized Systems Medicine Strategy to Tailor Treatments for Patients with Chemorefractory Acute Myeloid Leukemia

et al. 2013

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We present an individualized systems medicine (ISM) approach to optimize cancer drug therapies one patient at a time. ISM is based on (i) molecular profi ling and ex vivo drug sensitivity and resistance testing (DSRT) of patients' cancer cells to 187 oncology drugs, (ii) clinical implementation of therapies predicted to be effective, and (iii) studying consecutive samples from the treated patients to understand the basis of resistance. Here, application of ISM to 28 samples from patients with acute myeloid leukemia (AML) uncovered fi ve major taxonomic drug-response subtypes based on DSRT profi les, some with distinct genomic features (e.g., MLL gene fusions in subgroup IV and FLT3 -ITD mutations in subgroup V). Therapy based on DSRT resulted in several clinical responses. After progression under DSRT-guided therapies, AML cells displayed signifi cant clonal evolution and novel genomic changes potentially explaining resistance, whereas ex vivo DSRT data showed resistance to the clinically applied drugs and new vulnerabilities to previously ineffective drugs. SIGNIFICANCE:Here, we demonstrate an ISM strategy to optimize safe and effective personalized cancer therapies for individual patients as well as to understand and predict disease evolution and the next line of therapy. This approach could facilitate systematic drug repositioning of approved targeted drugs as well as help to prioritize and de-risk emerging drugs for clinical testing.

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“…Such screens can be useful for research purposes as well as in healthcare and can be difficult or impossible to perform using standard microplates. One example of such a screen is the drug sensitivity and resistance assay based on testing patient´s tumor cells against a library of anti-cancer compounds to predict optimal therapy for this particular patient [44][45][46] . Such assays performed in 96-or 384-well plates are restricted because of the limited patient´s tumor cell material available.…”

Section: Discussionmentioning

confidence: 99%

Droplet-microarray on superhydrophobic–superhydrophilic patterns for high-throughput live cell screenings

et al. 2016

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Cell-based high content phenotypic screenings are widely used in fundamental research, pharmaceutical industry, and healthcare to simultaneously evaluate the effects of multiple compounds or gene over-expressions/knockdown on the phenotype of cells. Most screenings, especially in the industrial sector, are performed using microplate technology, which relies on high reagents and cell consumption as well as on expensive liquid handling robotics. Developing miniaturized screening platforms has been an important topic in the past decade. In this study we demonstrate the applicability of the Droplet-Microarray platform based on superhydrophobic-superhydrophilic patterning for cell-based high throughput screenings. We show the homogeneous seeding of cells and culturing of different adherent cell lines in individual droplets of different sizes. We demonstrate pipetting-free medium exchange enabling cell cultures in miniaturized droplet arrays for up to 5 days. We establish the method of reverse transfection and reverse drug screenings in individual nanoliter-size droplets by printing the transfection mixtures or drug molecules directly onto superhydrophilic spots prior to cell seeding.

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Promising survival for patients with glioblastoma multiforme treated with individualised chemotherapy based on in vitro drug sensitivity testing

Cited by 27 publications

References 24 publications

In vitro sensitivity testing of minimally passaged and uncultured gliomas with TRAIL and/or chemotherapy drugs

In vitro sensitivity testing of minimally passaged and uncultured gliomas with TRAIL and/or chemotherapy drugs

Individualized Systems Medicine Strategy to Tailor Treatments for Patients with Chemorefractory Acute Myeloid Leukemia

Droplet-microarray on superhydrophobic–superhydrophilic patterns for high-throughput live cell screenings

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