Abstract
The advent of personalized cancer treatment resulted in the shift from the administration of cytotoxic drugs with broad activity spectrum to a targeted tumor-specific therapy. Aligned to this development, the focus of this study revolved around the application of our novel and patented microtube array membrane (MTAM) in the US National Cancer Institute (NCI) developed an HFA (hollow fiber assay) assay; hereinafter known as MTAM/HFA. Electrospun poly-L-lactic acid (PLLA) MTAM was sterilized and loaded with cell lines/patient derived tumor cells (PDTC) and subcutaneously implanted into the backs of BALB/C mice. Anticancer drugs were administered at the respective time points and the respective MTAMs were retrieved and the viability tumor cells within were quantified with the MTT assay. Results revealed that the MTAMs were excellent culture substrate for various cancer cell lines and PDTCs (patient derived tumor cells). Compared to traditional HFA systems that utilize traditional hollow fibers, MTAM/HFA revealed superior drug sensitivity for a wide range of anticancer drug classes. Additionally, the duration for each test was <14 days; all this while capable of producing similar trend outcome to the current gold-standard xenograft models. These benefits were observed in both the in vitro and in vivo stages, making it a highly practical phenotypic-based solution that could potentially be applied in personalized medicine.
Highlights
The development of anticancer drug research are often plagued with poor translatability between the developmental phases and the clinical phases [1]
The poly-L-lactic acid (PLLA) microtube array membrane (MTAM) appeared transparent under the optical microscope and the cells cultivated on the inner lumen surface appeared to be attached to it (Figure 1b)
The results demonstrate that our novel hollow fiber tube can be used to culture cancer cell lines
Summary
The development of anticancer drug research are often plagued with poor translatability between the developmental phases and the clinical phases [1]. The lack of heterogeneity in induced tumor models employed in the research and development phases further aggravates the poor translatability of outcome between various development phases [2,3]. Various research have demonstrated that there are correlations between PDX models and the corresponding clinical outcomes [9,10,11,12]; with growing number of research groups advocating the integration PDX models into current treatment of cancer patients in predicting clinical response [13,14] In line with this development, large scale in vivo anticancer drug screening in 60 treatment regimens against a comprehensive collection of PDX models (1075 models across 15 cancer types) have successfully duplicated treatment response of previous clinical trials [15]. Extensive analysis on a larger and more heterogeneous patient population has revealed similar degree of accuracy [16] In view of these outcomes, strong emphasis has been placed in the development of PDX models in anticancer drug screening
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