Sarcoma Spheroids and Organoids-Promising Tools in the Era of Personalized Medicine

Abstract

Cancer treatment is rapidly evolving toward personalized medicine, which takes into account the individual molecular and genetic variability of tumors. Sophisticated new in vitro disease models, such as three-dimensional cell cultures, may provide a tool for genetic, epigenetic, biomedical, and pharmacological research, and help determine the most promising individual treatment. Sarcomas, malignant neoplasms originating from mesenchymal cells, may have a multitude of genomic aberrations that give rise to more than 70 different histopathological subtypes. Their low incidence and high level of histopathological heterogeneity have greatly limited progress in their treatment, and trials of clinical sarcoma are less frequent than trials of other carcinomas. The main advantage of 3D cultures from tumor cells or biopsy is that they provide patient-specific models of solid tumors, and they overcome some limitations of traditional 2D monolayer cultures by reflecting cell heterogeneity, native histologic architectures, and cell-extracellular matrix interactions. Recent advances promise that these models can help bridge the gap between preclinical and clinical research by providing a relevant in vitro model of human cancer useful for drug testing and studying metastatic and dormancy mechanisms. However, additional improvements of 3D models are expected in the future, specifically the inclusion of tumor vasculature and the immune system, to enhance their full ability to capture the biological features of native tumors in high-throughput screening. Here, we summarize recent advances and future perspectives of spheroid and organoid in vitro models of rare sarcomas that can be used to investigate individual molecular biology and predict clinical responses. We also highlight how spheroid and organoid culture models could facilitate the personalization of sarcoma treatment, provide specific clinical scenarios, and discuss the relative strengths and limitations of these models.

Keywords: personalized medicine; precision medicine; sarcomas; spheroids; tumor microenvironment.

Figure 1

Workflow from biopsy to personalized medicine. From biopsy, it is possible obtain organoid and spheroid models that are sources of patient-specific DNA, RNA, and proteins (omics profiling). Patient omics may help in connecting genotype to phenotype, in order to select specific mutations, genes, and proteins and identify targets. Spheroids may be directly used for patient drug sensitivity screening and target validation. Integrating omics data and high-throughput drug screening can provide specific molecular and clinical scenarios for better personalized therapy.