A short-term three dimensional culture-based drug sensitivity test is feasible for malignant bone tumors.
Hiroaki GotoTakashi OhtsuMieko ItoMaiko SagisakaTakuya NarutoJun-Ichi NagaiNorihiko KitagawaMio TanakaMasakatsu YanagimachiYukihiko HiroshimaYohei MiyagiPublished in: Human cell (2023)
The feasibility of a short-term, three-dimensional (3D) culture-based drug sensitivity test (DST) for surgically resected malignant bone tumors, including osteosarcoma (OS), was evaluated utilizing two OS cell line (KCS8 or KCS9)-derived xenograft (CDX) models. Twenty-three (KCS8) or 39 (KCS9) of 60 tested drugs were likely effective in OS cells derived from a cell line before xenografting. Fewer drugs (19: KCS8, 26: KCS9) were selected as effective drugs in cells derived from a CDX tumor, although the drug sensitivities of 60 drugs significantly correlated between both types of samples. The drug sensitivity of a CDX tumor was not significantly altered after the depletion of non-tumorous components in the sample. In a surgically resected metastatic tumor obtained from a patient with OS, for whom a cancer genome profiling test detected a pathogenic PIK3CA mutation, DST identified mTOR and AKT inhibitors as effective drugs. Of two CDX and six clinical samples of OS and Ewing's sarcoma, DST identified proteasome inhibitors (bortezomib, carfilzomib) and CEP-701 as potentially effective drugs in common. This unique method of in vitro drug testing using 3D-cell cultures is feasible in surgically resected tissues of metastatic malignant bone tumors.
Keyphrases
- drug induced
- induced apoptosis
- squamous cell carcinoma
- bone mineral density
- lymph node
- small cell lung cancer
- cell cycle arrest
- adverse drug
- cell proliferation
- single cell
- gene expression
- soft tissue
- emergency department
- stem cells
- multiple myeloma
- cell death
- oxidative stress
- papillary thyroid
- endoplasmic reticulum stress
- prognostic factors
- young adults
- bone marrow
- squamous cell