Application status and future prospects of the PDX model in lung cancer

Abstract

Lung cancer is one of the most prevalent, fatal, and highly heterogeneous diseases that, seriously threaten human health. Lung cancer is primarily caused by the aberrant expression of multiple genes in the cells. Lung cancer treatment options include surgery, radiation, chemotherapy, targeted therapy, and immunotherapy. In recent decades, significant progress has been made in developing therapeutic agents for lung cancer as well as a biomarker for its early diagnosis. Nonetheless, the alternative applications of traditional pre-clinical models (cell line models) for diagnosis and prognosis prediction are constrained by several factors, including the lack of microenvironment components necessary to affect cancer biology and drug response, and the differences between laboratory and clinical results. The leading reason is that substantial shifts accrued to cell biological behaviors, such as cell proliferative, metastatic, invasive, and gene expression capabilities of different cancer cells after decades of growing indefinitely in vitro. Moreover, the introduction of individualized treatment has prompted the development of appropriate experimental models. In recent years, preclinical research on lung cancer has primarily relied on the patient-derived tumor xenograft (PDX) model. The PDX provides stable models with recapitulate characteristics of the parental tumor such as the histopathology and genetic blueprint. Additionally, PDXs offer valuable models for efficacy screening of new cancer drugs, thus, advancing the understanding of tumor biology. Concurrently, with the heightened interest in the PDX models, potential shortcomings have gradually emerged. This review summarizes the significant advantages of PDXs over the previous models, their benefits, potential future uses and interrogating open issues.

Keywords: PDX model; co-clinical trials; lung cancer; personalized medicine; pre-clinical research.

Figure 1

HIS mouse production process.

Figure 2

Establishment process of PDX models.

Figure 3

The process of co-clinical trial.

Figure 4

The applications of pre-clinical models.