Novel hydrogels: are they poised to transform 3D cell-based assay systems in early drug discovery?

Treherne, J Mark; Miller, Aline F.

doi:10.1080/17460441.2023.2175813

Cited by 1 publication

(1 citation statement)

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“…It has been argued that the biological and phenotypic complexity of 3D cultures allows for more predictive assays of future clinical efficacy to be developed, as they are grown in a more physiological and/or pathological 3D environment [14]. In particular, the key role of 6 novel hydrogel scaffolds in mimicking this extracellular environment has been emphasized in transforming the physiological and therapeutic relevance of such 3D cellbased in vitro assay systems [15]. The microenvironment for tumor-like growth is of particular importance when testing new drugs, so that the data obtained can be better cross-correlated with in vivo studies.…”

Section: Introductionmentioning

confidence: 99%

3D culture of pancreatic cancer cellsin vitrorecapitulates an aberrant mitochondrial oxidative phosphorylation genotype observedin vivo

Kuś,

Mark Treherne,

Earnshaw

et al. 2024

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The treatment of many aggressive cancers remains a significant unmet medical need. An aberrant dependence of tumors on mitochondrial oxidative phosphorylation pathways has been well characterized in mediating the progression of pancreatic cancers, as well as some other malignancies. However, the discovery and development of new therapeutic strategies targeting or manipulating this pathway in pancreatic tumors has been relatively slow when compared with other cancers, limiting the current options for treating patients. One key technical challenge in discovering new therapies has been the limited ability of cancer cell lines when grown in 2D conditions to recapitulate the mitochondrial oxidative phosphorylation pathways in vitro that have been observed in vivo. In part, this is because 2D cultures fail to mimic the extracellular 3D tumoral environment. More generally, the translation of data based on 2D pancreatic cancer cell culture systems have also been constraining options for discovering new therapies. Conversely, 3D cultures can provide an improved technology platform in which pathologically relevant pathways in tumors can be recapitulated and analyzed in vitro. In this study, we have demonstrated in 3D cultures the reconstruction of the mitochondrial oxidative phosphorylation genotype in vitro, which more closely resembles that observed in vivo. Our study highlights the value of using transcriptomic readouts as a method to demonstrate the relevance and utility of 3D preclinical models in vitro, when grown in a more physiological extracellular environment. This key technological advance can now better enable the discovery and subsequent development of new therapeutic strategies targeting disease-relevant pathways found in pancreatic and other tumors.

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Section: Introductionmentioning

confidence: 99%