Advanced Cell Culture Techniques for Cancer Drug Discovery

Lovitt, Carrie J.; Shelper, Todd; Avery, Vicky M.

doi:10.3390/biology3020345

Cited by 230 publications

(231 citation statements)

References 96 publications

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“…Firstly, the 3D structure of MCTS reduces the number of cancer cells exposed to anticancer agents; these drugs have more accessibility to cells in monolayer culture (Carrie J. Lovitt, 2014). Secondly, the tightly adhered cells and ECM in MCTS can limit drug penetration (Frankel et al, 2000).…”

Section: Why 3d Culture?mentioning

confidence: 99%

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Concise Review: 3D cell culture systems for anticancer drug screening

2016

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Abstract- cultures are becoming increasingly popular due to their ability to mimic tissuelike structures more effectively than monolayer cultures. In cancer research, the natural tumor characteristics and architecture are more closely mimicked by 3D cell models. Thus, 3D cell cultures are more promising and suitable models, particularly for in vitro drug screening to predict in vivo efficacy. Different methods have been developed to create 3D cell culture systems for research application. This review will introduce and discuss 3D cell culture methods most popularly used in drug screening. The potential applications of these systems in anticancer drug screening will also be discussed.

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Section: Why 3d Culture?mentioning

confidence: 99%

“…The primary disadvantage of a 2D system is that it does not mimic an actual 3D tumor and is not biologically relevant (Carrie J. Lovitt, 2014). Cells in the in vivoenvironment usually interact with neighboring cells and the extracellular matrix (ECM); however, 2D cell models cannot recapitulate those characteristics.…”

Section: Introductionmentioning

confidence: 99%

Concise Review: 3D cell culture systems for anticancer drug screening

2016

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“…[23][24][25][26] There are many inherent differences in the sensitivity and efficacy of chemotherapeutics between 2D and 3D culture models. [27][28][29] Using a 2D model, it is difficult to elucidate the subtleties of the nanoparticles' interaction with tumor biology; for example, the depth of penetrance into the tumor structure, differences in localization and cellular uptake, and efficacy of photothermal treatment cannot be fully appreciated when using a monolayer system. Furthermore, 3D culture models provide a platform that more closely mimics the complex and dynamic tumor microenvironment compared to conventional 2D cultures.…”

Section: Crawford Et Almentioning

confidence: 99%

Photothermal ablation of inflammatory breast cancer tumor emboli using plasmonic gold nanostars

Crawford¹,

Shammas²,

Fales³

et al. 2017

IJN

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Inflammatory breast cancer (IBC) is rare, but it is the most aggressive subtype of breast cancer. IBC has a unique presentation of diffuse tumor cell clusters called tumor emboli in the dermis of the chest wall that block lymph vessels causing a painful, erythematous, and edematous breast. Lack of effective therapeutic treatments has caused mortality rates of this cancer to reach 20%–30% in case of women with stage III–IV disease. Plasmonic nanoparticles, via photothermal ablation, are emerging as lead candidates in next-generation cancer treatment for site-specific cell death. Plasmonic gold nanostars (GNS) have an extremely large two-photon luminescence cross-section that allows real-time imaging through multiphoton microscopy, as well as superior photothermal conversion efficiency with highly concentrated heating due to its tip-enhanced plasmonic effect. To effectively study the use of GNS as a clinically plausible treatment of IBC, accurate three-dimensional (3D) preclinical models are needed. Here, we demonstrate a unique in vitro preclinical model that mimics the tumor emboli structures assumed by IBC in vivo using IBC cell lines SUM149 and SUM190. Furthermore, we demonstrate that GNS are endocytosed into multiple cancer cell lines irrespective of receptor status or drug resistance and that these nanoparticles penetrate the tumor embolic core in 3D culture, allowing effective photothermal ablation of the IBC tumor emboli. These results not only provide an avenue for optimizing the diagnostic and therapeutic application of GNS in the treatment of IBC but also support the continuous development of 3D in vitro models for investigating the efficacy of photothermal therapy as well as to further evaluate photothermal therapy in an IBC in vivo model.

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“…Although challenges exist around the predictive value of preclinical cellular models, recent advances in high-content screening technologies and the use of models that better reflect human disease such as 3D cell culture, 113 patient-derived primary cells, 114 cancer stem cells, 115,116 and co-culture systems 117 offer much promise for the future. 118 Providing there is a clear understanding of the cancer biology, including relevant pharmacodynamic biomarker(s) and/or phenotype(s), there may be a good rationale for using a well-designed cell-based screening cascade to run a drug discovery program. Indeed, a relevant pharmacodynamic biomarker often makes an effective primary assay for a mechanism-informed cell-based screen, allowing correlations between biomarker readout and phenotype to be demonstrated at an early stage.…”

Section: Cell-based Hts and Target Deconvolutionmentioning

confidence: 99%

Addressing the Right Targets in Oncology: Challenges and Alternative Approaches

Stock¹,

Jones²,

Hammonds³

et al. 2015

SLAS Discovery

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Translating existing and emerging knowledge of cancer biology into effective novel therapies remains a great challenge in drug discovery. A firm understanding of the target biology, confidence in the supporting preclinical research, and access to diverse chemical matter is required to lower attrition rates and prosecute targets effectively. Understanding past successes and failures will aid in refining this process to deliver further therapeutic benefit to patients. In this review, we suggest that early oncology drug discovery should focus on selection and prosecution of cancer targets with strong disease biology rather than on more chemically "druggable" targets with only modest disease-linkage. This approach offers higher potential benefit but also increases the need for innovative and alternative approaches. These include using different methods to validate novel targets and identify chemical matter, as well as raising the standards and our interpretation of the scientific literature. The combination of skills required for this emphasizes the need for broader early collaborations between academia and industry.

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Advanced Cell Culture Techniques for Cancer Drug Discovery

Cited by 230 publications

References 96 publications

Concise Review: 3D cell culture systems for anticancer drug screening

Concise Review: 3D cell culture systems for anticancer drug screening

Photothermal ablation of inflammatory breast cancer tumor emboli using plasmonic gold nanostars

Addressing the Right Targets in Oncology: Challenges and Alternative Approaches

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