The challenge of developing robust drugs to overcome resistance

Anderson, Amy C.; Pollastri, Michael P.; Schiffer, Celia A.; Peet, Norton P.

doi:10.1016/j.drudis.2011.07.001

Cited by 17 publications

(13 citation statements)

References 82 publications

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“…However, it is likely that heterogeneity and cooperation of cancer cells in patient tumours drives tumour invasion through remodelling of the extracellular matrix ( Chapman et al , 2014). Thus, cancer is represented by cells that vary in their proliferative, invasive and metastatic phenotype, which contributes both to tumour growth and also emergence of drug resistance ( Anderson et al , 2011). However, it is often not feasible to investigate the effect of tumour cell heterogeneity in mouse xenograft models as large numbers of patient primary tumour cells are required for successful engraftment.…”

Section: Discussionmentioning

confidence: 99%

Embryonic zebrafish xenograft assay of human cancer metastasis

et al. 2018

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Cancer metastasis is the most important prognostic factor determining patient survival, but currently there are very few drugs or therapies that specifically inhibit the invasion and metastasis of cancer cells. Currently, human cancer metastasis is largely studied using transgenic and immunocompromised mouse xenograft models, which are useful for analysing end-point tumour growth but are unable to accurately and reliably monitor in vivo invasion, intravasation, extravasation or secondary tumour formation of human cancer cells. Furthermore, limits in our ability to accurately monitor early stages of tumour growth and detect micro-metastases likely results in pain and suffering to the mice used for cancer xenograft experiments. Zebrafish ( Danio rerio) embryos, however, offer many advantages as a model system for studying the complex, multi-step processes involved during cancer metastasis. This article describes a detailed method for the analysis of human cancer cell invasion and metastasis in zebrafish embryos before they reach protected status at 5 days post fertilisation. Results demonstrate that human cancer cells actively invade within a zebrafish microenvironment, and form metastatic tumours at secondary tissue sites, suggesting that the mechanisms involved during the different stages of metastasis are conserved between humans and zebrafish, supporting the use of zebrafish embryos as a viable model of human cancer metastasis. We suggest that the embryonic zebrafish xenograft model of human cancer is a tractable laboratory model that can be used to understand cancer biology, and as a direct replacement of mice for the analysis of drugs that target cancer invasion and metastasis.

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Section: Discussionmentioning

confidence: 99%

Embryonic zebrafish xenograft assay of human cancer metastasis

et al. 2018

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“…That the emergence of antimicrobial resistance is a challenge that must be faced urgently has been recently recognised [1] and, as a result, there is an ongoing need for new antibacterial drugs [2,3,4]. Unfortunately, this realisation has come at a time when the antibacterial pipeline is poorly populated [5], and key pharmaceutical players are exiting the area.…”

Section: Introductionmentioning

confidence: 99%

Fused-Ring Oxazolopyrrolopyridopyrimidine Systems with Gram-Negative Activity

et al. 2017

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“…infections. There are several reviews appeared in literature [10][11][12][13][14][15][16][17][18][19] describing the approaches to design the inhibitors of GyrB and ParE enzymes. High resolution structural information on GyrB and ParE has been instrumental in stimulating the research effort for new synthetic chemotypes that inhibits these enzymes but currently there are no compounds in the clinic.…”

Section: Introductionmentioning

confidence: 99%