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.

Systems approach for congruence and selection of cancer models towards precision medicine

“…However, they lack of immune system components and loss of stromal components over time represent limitations in representing the tumor microenvironment [ 67 ]. On the other hand, PDXs preserve the original tumor architecture and include stromal and at least some immune components [ 68 , 69 ], but again, PDX development and maintenance is time and resource intensive.…”

LUNGBANK: A Novel Biorepository Strategy Tailored for Comprehensive Multi-Omics Analysis and P-Medicine Applications in Lung Cancer

“…These classical methodologies remain indispensable for diagnosing and characterizing lung cancer, continuing to exert a profound influence over clinical decisions. Samples from our biorepository serve as a valuable resource for the development of PDC, PDO, and PDX models for the in vitro and in vivo analyses of lung cancer biology, as well as personalized therapeutic screening ( Ibarrola-Villava et al, 2018 ; Kim et al, 2019a ; Kim et al, 2019b ; Kita et al, 2019 ; Liu et al, 2023 ). These cultured entities not only epitomize the versatility and diversity within biobanking practices but also stand as a considerable reservoir of living biobanks, offering invaluable insights and opportunities for research across a spectrum of medical and scientific domains.…”