Drug sensitivity testing of patient-derived bone sarcomas identifies selective kinase inhibitors for patients with refractory disease
Ex vivo drug sensitivity testing of patient‑derived bone sarcoma cells can rapidly identify specific kinase inhibitors that are effective for patients with refractory disease, enabling personalized therapeutic strategies.
This study aimed to investigate the feasibility and predictive value in performing ex vivo drug sensitivity testing on bone sarcomas from patients with refractory disease and identify agents with potential therapeutic benefit. A cohort of 7 osteosarcomas (OS) and 4 Ewing sarcoma (ES) patient‑derived cells (PDCs) were screened against a library of oncological drugs, gene panel sequencing and mRNA expression arrays. Drug responses were correlated to the molecular characteristics of specific sarcoma subtypes and patient response to therapy. OS PDCs showed heterogeneous drug sensitivity, with observed responses for mTOR, PKC, MAPK and CDK inhibitors that correlated with the histological subtype and genotype of the primary tumor. Two of 4 ES PDCs displayed morphological dichotomy as separate Ews‑Fli1 positive spheroid and adherent populations. These ES PDCs showed comparable responses to most of the oncological drugs but differential sensitivity to rapalogs and SMAC‑mimetics. In both, OS and ES, the drug sensitivity of PDCs correlated to the patient response to chemotherapy. Drug sensitivity testing of PDCs from bone sarcomas is a valuable tool for a rapid identification of potential treatments, in otherwise genetically complex group of tumors where genome‑based assays are difficult to implement.
Bone sarcomas such as osteosarcoma and Ewing sarcoma have high genomic complexity and limited targeted therapy options. By profiling patient‑derived cells ex vivo, clinicians can identify effective kinase inhibitors tailored to the individual tumor’s molecular profile, potentially improving outcomes for patients with refractory disease.
Bizonyítékszint: Korai humán adat. Kis vagy feltáró emberi adat.
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