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An Organotypic High Throughput System for Characterization of Drug Sensitivity of Primary Multiple Myeloma Cells
Published on: July 15, 2015
A short-term three dimensional culture-based drug sensitivity test is feasible for malignant bone tumors
Hiroaki Goto1,2, Takashi Ohtsu3,4, Mieko Ito5
1Division of Hematology/Oncology, Kanagawa Children's Medical Center, 2-138-4 Mutsukawa Minami-Ku, Yokohama, 232-8555, Japan. hgoto3949@gmail.com.
Abstract:
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.
Insights
A novel 3D culture drug sensitivity test (DST) shows promise for malignant bone tumors. This method accurately predicts effective cancer drugs using patient tumor samples, aiding personalized treatment strategies.
Area of Science:
- Oncology
- Biotechnology
- Pharmacology
Background:
- Malignant bone tumors like osteosarcoma (OS) present treatment challenges.
- Predicting drug efficacy in bone tumors is crucial for effective therapy.
- Current drug sensitivity testing methods may not fully represent in vivo tumor conditions.
Purpose of the Study:
- To evaluate the feasibility of a short-term, 3D culture-based drug sensitivity test (DST) for surgically resected malignant bone tumors.
- To assess the correlation of drug sensitivity between cell line-derived xenografts (CDX) and patient-derived samples.
- To identify potentially effective drugs for osteosarcoma and other bone sarcomas.
Main Methods:
- Utilized two osteosarcoma cell line (KCS8, KCS9)-derived xenograft (CDX) models for drug screening.
- Performed 3D culture-based drug sensitivity testing on CDX models and surgically resected clinical samples.
- Analyzed drug sensitivity profiles of 60 tested drugs across different sample types.
Main Results:
- A significant correlation was observed in drug sensitivities between cell line and CDX-derived samples.
- DST identified specific effective drugs for osteosarcoma, including mTOR and AKT inhibitors for a PIK3CA-mutated tumor.
- Commonly effective drugs, such as proteasome inhibitors, were identified across CDX and clinical samples of OS and Ewing's sarcoma.
Conclusions:
- A 3D culture-based drug sensitivity test is feasible for surgically resected malignant bone tumors.
- This in vitro method shows potential for guiding personalized drug selection in bone cancer treatment.
- The DST approach can identify common and specific drug sensitivities in diverse bone sarcoma samples.
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