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Mol Pharm. 2014 Jul 7;11(7):2040-50. doi: 10.1021/mp500085p. Epub 2014 Apr 29.

Hydrogel-based 3D model of patient-derived prostate xenograft tumors suitable for drug screening.

Author information

1
Departments of Biochemistry and Cell Biology and ‡Bioengineering, Rice University , Houston, Texas 77005, United States.

Abstract

The lack of effective therapies for bone metastatic prostate cancer (PCa) underscores the need for accurate models of the disease to enable the discovery of new therapeutic targets and to test drug sensitivities of individual tumors. To this end, the patient-derived xenograft (PDX) PCa model using immunocompromised mice was established to model the disease with greater fidelity than is possible with currently employed cell lines grown on tissue culture plastic. However, poorly adherent PDX tumor cells exhibit low viability in standard culture, making it difficult to manipulate these cells for subsequent controlled mechanistic studies. To overcome this challenge, we encapsulated PDX tumor cells within a three-dimensional hyaluronan-based hydrogel and demonstrated that the hydrogel maintains PDX cell viability with continued native androgen receptor expression. Furthermore, a differential sensitivity to docetaxel, a chemotherapeutic drug, was observed as compared to a traditional PCa cell line. These findings underscore the potential impact of this novel 3D PDX PCa model as a diagnostic platform for rapid drug evaluation and ultimately push personalized medicine toward clinical reality.

PMID:
24779589
PMCID:
PMC4096229
DOI:
10.1021/mp500085p
[Indexed for MEDLINE]
Free PMC Article

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