4.7 Article

A comparative study of tumour-on-chip models with patient-derived xenografts for predicting chemotherapy efficacy in colorectal cancer patients

Journal

Publisher

FRONTIERS MEDIA SA
DOI: 10.3389/fbioe.2022.952726

Keywords

organ-on-chip (OoC); PDX (patient derived xenograft); dose response; 3D culture; in vivo

Funding

  1. Ministry of Education [R-397-000-298-114]
  2. Singapore-MIT Alliance for Research and Technology (SMART) [ING-000534 BIO]
  3. Australian Research Council [FT180100157, DP200101658]
  4. Biomedical Research Council (BMRC) [SPF 2015/002]
  5. Agency for Science, Technology and Research
  6. National Medical Research Council (NMRC) [CIRG/1439/2015]
  7. Australian Research Council [DP200101658, FT180100157] Funding Source: Australian Research Council

Ask authors/readers for more resources

Inter-patient and intra-tumour heterogeneity have led to the need for personalized cancer therapy. Patient-derived xenograft (PDX) models are specific to individual patients, but they are not cost-effective and scalable. Tumour Organ-on-Chip (OoC) models can replicate aspects of the 3D tumour microenvironment and can be used for drug screening. However, there is limited validation to compare drug responses between tumour OoCs and PDX models.
Inter-patient and intra-tumour heterogeneity (ITH) have prompted the need for a more personalised approach to cancer therapy. Although patient-derived xenograft (PDX) models can generate drug response specific to patients, they are not sustainable in terms of cost and time and have limited scalability. Tumour Organ-on-Chip (OoC) models are in vitro alternatives that can recapitulate some aspects of the 3D tumour microenvironment and can be scaled up for drug screening. While many tumour OoC systems have been developed to date, there have been limited validation studies to ascertain whether drug responses obtained from tumour OoCs are comparable to those predicted from patient-derived xenograft (PDX) models. In this study, we established a multiplexed tumour OoC device, that consists of an 8 x 4 array (32-plex) of culture chamber coupled to a concentration gradient generator. The device enabled perfusion culture of primary PDX-derived tumour spheroids to obtain dose-dependent response of 5 distinct standard-of-care (SOC) chemotherapeutic drugs for 3 colorectal cancer (CRC) patients. The in vitro efficacies of the chemotherapeutic drugs were rank-ordered for individual patients and compared to the in vivo efficacy obtained from matched PDX models. We show that quantitative correlation analysis between the drug efficacies predicted via the microfluidic perfusion culture is predictive of response in animal PDX models. This is a first study showing a comparative framework to quantitatively correlate the drug response predictions made by a microfluidic tumour organ-on-chip (OoC) model with that of PDX animal models.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.7
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

No Data Available
No Data Available