Patient-derived tumor models and their distinctive applications in personalized drug therapy

Abstract

Tumor models in vitro are conventional methods for developing anti-cancer drugs, evaluating drug delivery, or calculating drug efficacy. However, traditional cell line-derived tumor models are unable to capture the tumor heterogeneity in patients or mimic the interaction between tumors and their surroundings. Recently emerging patient-derived preclinical cancer models, including of patient-derived xenograft (PDX) model, circulating tumor cell (CTC)-derived model, and tumor organoids-on-chips, are promising in personalized drug therapy by recapitulating the complexities and personalities of tumors and surroundings. These patient-derived models have demonstrated potential advantages in satisfying the rigorous demands of specificity, accuracy, and efficiency necessary for personalized drug therapy. However, the selection of suitable models is depending on the specific therapeutic requirements dictated by cancer types, progressions, or the assay scale. As an example, PDX models show remarkable advantages to reconstruct solid tumors in vitro to understand drug delivery and metabolism. Similarly, CTC-derived models provide a sensitive platform for drug testing in advanced-stage patients, while also facilitating the development of drugs aimed at suppressing tumor metastasis. Meanwhile, the demand for large-scale testing has promoted the development of tumor organoids-on-chips, which serves as an optimal tool for high-throughput drug screening. This review summarizes the establishment and development of PDX, CTC-derived models, and tumor organoids-on-chips and addresses their distinctive advantages in drug discovery, sensitive testing, and screening, which demonstrate the potential to aid in the selection of suitable models for fundamental cancer research and clinical trials, and further developing the personalized drug therapy.

Keywords: Circulating tumor cell-derived model; Patient-derived xenograft model; Personalized drug therapy; Tumor organoids-on-chips.

Fig. 1

Diagram showing the construction and application of the PDX models. The PDX models were constructed by transplanting patient-derived tumor tissue into immunodeficient mice or humanized immune deficient mice. The PDX models were applied to explore tumor function data and identify optimal therapeutics using PDX mouse clinical trials.

Fig. 2

Circulating tumor cell (CTC) enrichment techniques. Current devices/methods used to enrich and isolate CTC exploit physical properties (i.e., electric charge, size, density and deformability) or biological properties (including positive and negative selection) to differentiate CTC from blood cells.

Fig. 3

Construction and application of organoids and organoids-on-chips. Sort and enrich stem cells in functional units, and then induce differentiation into organoid models in culture medium, or plant them in organ-on-chip, which can maximize the simulation of the in vivo environment. Both of the above models play an important role in early drug development, preclinical trial and translation, or high-throughput drug screening and test.