Empowering personalized medicine: unleashing the potential of patient-derived explants in clinical practice

Abstract

In recent decades, significant progress has been made in understanding the molecular characteristics of cancer and its microenvironment, leading to the development of life-saving treatments. However, patients often experience side effects from standard therapies, highlighting the need for personalized medicine. Personalized medicine aims to customize drug therapy and preventive care based on individual patients' specific requirements. The heterogeneity within tumors and among patients necessitates personalized medicine approaches. Patient-derived organoids (PDOs), xenografts (PDXs), and explants (PDEs) have emerged as valuable models for studying tumor behaviour and drug response. This paper aims to summarize the latest advancements in patient-derived explants, focusing on their potential utility in the clinic. Different methods for culturing PDEs, including the free-floating approach, the grid method, and sponge scaffolds, are discussed. These approaches provide opportunities for long-term viability, oxygen and nutrient supply, and maintenance of tissue integrity. Additionally, various solid tumor models using PDEs are highlighted, together with assays to study PDE viability, characteristics, and response to drug treatment.

Keywords: individual therapy; oncology; patient-derived explants; personalized medicine.

Table 1. A summary of available methods of PDE culture, including their characteristic features, advantages and drawbacks. Choosing the most suitable method for patient-derived explant culture will depend on the specific research objectives, the cultured tissue type, and the desired level of experimental control and tissue preservation. Researchers often tailor their approach to achieve optimal study outcomes based on these factors.

Table 2. PDE culture models, methods and their application in some solid tumors

Figure 1. Three types of PDE models. A) Tissue fragments are entirely submerged in a medium and float freely, often combined with rotation on a shaker; B) Specimens are cultured on a metal grid, having contact with a medium and air, culture of tissue slices or cubes; C) Tissue fragments are placed on the sponge scaffold to provide simultaneous nutrient and oxygen supply. Figure created with BioRender.

Figure 2. Applications of PDE models in research. Explants are the most commonly used in cancer research to test and validate various therapies considering personalized approach and tumor heterogeneity. PDEs are also valuable in biomarker discovery associated with different diseases, often leading to new drug development. Moreover, due to their unique properties, PDEs are bridging the gap between research and clinics.