Chordomas are rare tumors that originate in the chordochon and most often occur in the sacral bone or base of the skull. Chordomas are not considered sensitive to conventional chemotherapy, and their rarity makes it very difficult for general experiments to determine an effective treatment. Therefore, it is necessary to discover new treatments. Patient-derived organoids can accelerate drug discovery and development studies and predict patient response to treatment.
Recently, researchers at the University of California in the United States in Sci. In the journal Adv, titled "Personalized chordoma organoids for drug discovery studies, Personalized Chordoma Organoids for Drug Discovery Studies," researchers successfully established an organoid model from 7 chordoma samples from 5 patients of different sites and stages of the disease that could be rapidly established and effectively screened to aid drug discovery.
First, researchers began routinely establishing viable, manageable models of chordoma organs from tissues obtained from different surgical procedures (primary resection, metastasection, and biopsy; ),anatomical site (cervical, thoracic or lumbar spine, sacral bone, and pelvis), and disease characteristics (primary, recurrent, or metastatic chordoma). Tumor tissue is broken down into a cell suspension containing single cells and small cell clusters. The researchers obtained enough cells in all cases and established living tissue organoids for identification and screening for all samples.
To verify that the organoid model in the study was suitable for high-throughput screening of chordomas, the researchers screened 230 compounds for drug discovery at single concentrations on an organoid model. Two drug molecules, gefitinib and imatinib, were eventually identified as drug candidates for the treatment of certain chordomas.
Histologic and immunohistological features of chordoma specimens and their derived organoids
Image source: https://www.science.org/doi/epdf/10.1126/sciadv.abl3674
Due to the natural history and slow growth rate of chordoma, determining the clinical efficacy of new treatments is challenging. However, in this study, the researchers established an organoid model of chordoma from different tumor sites and histology, and this personalized chordoma model can be quickly established and effectively screened in vitro to identify pathways sensitive to interference, and to facilitate the development of drug molecules, which not only improves the treatment effect, but also avoids ineffective treatment and its related toxic side effects.
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Ahmad Al Shihabi et al. Personalized chordoma organoids for drug discovery studies. Sci Adv. 2022 Feb 18;8( 7):eabl3674. doi: 10.1126/sciadv.abl3674.