A multidimensional impedance platform for the real-time analysis of single and combination drug pharmacology in patient-derived viable melanoma models

Seidel, Daniel; Rothe, R; Kirsten, Mandy; Jahnke, Heinz‐Georg; Dumann, Konstantin; Ziemer, Mirjana; Simon, Jan‐Christoph; Robitzki, Andrea A.

doi:10.1016/j.bios.2018.08.049

Cited by 16 publications

(18 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In accordance with clinical observations [48], approximately 60% of the BRAF mutated tumors responded in the 3D assay. In agreement with a recent study, in which melanoma tissue was cultured as micro tumor fragments [49], complete loss of viability following BRAF or MEK inhibition was, however, not achieved, a finding that may be explained by intra-tumor heterogeneity and/or the presence of normal cell infiltration.…”

Section: Discussionsupporting

confidence: 91%

“…Both pre-clinical and clinical studies have demonstrated that combined BRAF and MEK inhibition may be beneficial for patients with BRAF mutated tumors. Moreover, selective MEK inhibition has shown efficacy in NRAS mutated melanoma (reviewed in [49]). In the current study, response of BRAF mutated tumors to Vemurafenib and/or Cobimetinib was in most cases comparable, and in accordance with previous studies [50], half of the NRAS mutated tumors responded to MEK inhibition.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

A Three-dimensional Ex Vivo Viability Assay Reveals a Strong Correlation Between Response to Targeted Inhibitors and Mutation Status in Melanoma Lymph Node Metastases

Flørenes

Flem-Karlsen

McFadden

et al. 2019

Translational Oncology

View full text Add to dashboard Cite

Although clinical management of melanoma has changed considerably in recent years, intrinsic treatment resistance remains a severe problem and strategies to design personal treatment regimens are highly warranted. We have applied a three-dimensional (3D) ex vivo drug efficacy assay, exposing disaggregated cells from 38 freshly harvested melanoma lymph node metastases and 21 patient derived xenografts (PDXs) to clinical relevant drugs for 7 days, and examined its potential to evaluate therapy response. A strong association between Vemurafenib response and BRAF mutation status was achieved ( P < .0001), while enhanced viability was seen in some NRAS mutated tumors. BRAF and NRAS mutated tumors responded comparably to the MEK inhibitor Cobimetinib. Based on the ex vivo results, two tumors diagnosed as BRAF wild-type by routine pathology examinations had to be re-evaluated; one was subsequently found to have a complex V600E mutation, the other a double BRAF mutation (V600E/K601 N). No BRAF inhibitor resistance mechanisms were identified, but PIK3CA and NF1 mutations were identified in two highly responsive tumors. Concordance between ex vivo drug responses using tissue from PDXs and corresponding patient tumors demonstrate that PDX models represent an indefinite source of tumor material that may allow ex vivo evaluation of numerous drugs and combinations, as well as studies of underlying molecular mechanisms. In conclusion, we have established a rapid and low cost ex vivo drug efficacy assay applicable on tumor tissue from patient biopsies. The 3D/spheroid format, limiting the influence from normal adjacent cells and allowing assessment of drug sensitivity to numerous drugs in one week, confirms its potential as a supplement to guide clinical decision, in particular in identifying non-responding patients.

show abstract

Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

A Three-dimensional Ex Vivo Viability Assay Reveals a Strong Correlation Between Response to Targeted Inhibitors and Mutation Status in Melanoma Lymph Node Metastases

Flørenes

Flem-Karlsen

McFadden

et al. 2019

Translational Oncology

View full text Add to dashboard Cite

show abstract

“…Single cell or few cell populations [16], large cell populations, and three-dimensional (3D) cell aggregates, such as cell spheroids [17,18], have been tested. A recent report by Seidel et al [19] focused on the evaluation of derived two-dimensional (2D) and 3D cell cultures with original patient undissociated melanoma tissues in order to develop cell model data of combined targeted cancer therapy and to transfer these data to an in vivo situation [19]. Figure 2 shows the correlation of chemosensitivity and drug kinetics obtained by cell impedance and by standard ATP assay on the different cell cultures.…”

Section: Impedance-based Methods For Cell Monitoringmentioning

confidence: 99%

“…3 targeted cancer therapy and to transfer these data to an in vivo situation [19]. Figure 2 shows the correlation of chemosensitivity and drug kinetics obtained by cell impedance and by standard ATP assay on the different cell cultures.…”

Section: Impedance-based Methods For Cell Monitoringmentioning

confidence: 99%

See 1 more Smart Citation

Label-Free Bioelectrochemical Methods for Evaluation of Anticancer Drug Effects at a Molecular Level

Tadini‐Buoninsegni

Palchetti

2020

Sensors

View full text Add to dashboard Cite

Cancer is a multifactorial family of diseases that is still a leading cause of death worldwide. More than 100 different types of cancer affecting over 60 human organs are known. Chemotherapy plays a central role for treating cancer. The development of new anticancer drugs or new uses for existing drugs is an exciting and increasing research area. This is particularly important since drug resistance and side effects can limit the efficacy of the chemotherapy. Thus, there is a need for multiplexed, cost-effective, rapid, and novel screening methods that can help to elucidate the mechanism of the action of anticancer drugs and the identification of novel drug candidates. This review focuses on different label-free bioelectrochemical approaches, in particular, impedance-based methods, the solid supported membranes technique, and the DNA-based electrochemical sensor, that can be used to evaluate the effects of anticancer drugs on nucleic acids, membrane transporters, and living cells. Some relevant examples of anticancer drug interactions are presented which demonstrate the usefulness of such methods for the characterization of the mechanism of action of anticancer drugs that are targeted against various biomolecules.

show abstract

Advanced Materials and Sensors for Microphysiological Systems: Focus on Electronic and Electrooptical Interfaces

2022

View full text Add to dashboard Cite

Advanced in vitro cell culture systems or microphysiological systems (MPSs), including microfluidic organ‐on‐a‐chip (OoC), are breakthrough technologies in biomedicine. These systems recapitulate features of human tissues outside of the body. They are increasingly being used to study the functionality of different organs for applications such as drug evolutions, disease modeling, and precision medicine. Currently, developers and endpoint users of these in vitro models promote how they can replace animal models or even be a better ethically neutral and humanized alternative to study pathology, physiology, and pharmacology. Although reported models show a remarkable physiological structure and function compared to the conventional 2D cell culture, they are almost exclusively based on standard passive polymers or glass with none or minimal real‐time stimuli and readout capacity. The next technology leap in reproducing in vivo‐like functionality and real‐time monitoring of tissue function could be realized with advanced functional materials and devices. This review describes the currently reported electronic and optical advanced materials for sensing and stimulation of MPS models. In addition, an overview of multi‐sensing for Body‐on‐Chip platforms is given. Finally, one gives the perspective on how advanced functional materials could be integrated into in vitro systems to precisely mimic human physiology.

show abstract

A multidimensional impedance platform for the real-time analysis of single and combination drug pharmacology in patient-derived viable melanoma models

Cited by 16 publications

References 45 publications

A Three-dimensional Ex Vivo Viability Assay Reveals a Strong Correlation Between Response to Targeted Inhibitors and Mutation Status in Melanoma Lymph Node Metastases

A Three-dimensional Ex Vivo Viability Assay Reveals a Strong Correlation Between Response to Targeted Inhibitors and Mutation Status in Melanoma Lymph Node Metastases

Label-Free Bioelectrochemical Methods for Evaluation of Anticancer Drug Effects at a Molecular Level

Advanced Materials and Sensors for Microphysiological Systems: Focus on Electronic and Electrooptical Interfaces

Contact Info

Product

Resources

About