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A Novel Anionic-phosphate-platinum Complex Effectively Targets a Cisplatinum-resistant Osteosarcoma in a
Kentaro Igarashi1,2,3, Kei Kawaguchi1,2, Norio Yamamoto3
1AntiCancer, Inc., San Diego, CA, U.S.A.
Background/Aim:
We have previously developed a novel bone-targeting platinum compound, 3Pt, and showed that it has strong inhibitory activity against osteosarcoma cells and orthotopic cell-line xenograft mouse models. In the present report, we compared the efficacy of 3Pt to cisplatinum (CDDP) in a CDDP-resistant relapsed osteosarcoma patient-derived orthotopic xenograft (PDOX) mouse model.
Patients And Methods:
The tumor of a patient with osteosarcoma of the distal femur was treated with CDDP-based chemotherapy followed by surgery. The surgical specimen was used to establish a PDOX model. An osteosarcoma cell line was also established from the original patient tumor. Osteosarcoma cell viability was assessed with the WST-8 assay and the IC50 values were calculated. The PDOX models were randomized into three groups: untreated control, CDDP-treated group, and 3Pt-treated group. Tumor size and body weight were measured twice a week.
Results:
3Pt had a strong concentration-dependent cytocidal effect in vitro. The IC50 value of 3Pt was significantly lower than that of CDDP. On day 14 of the treatment, 3Pt caused a significantly greater tumor growth inhibition compared to the untreated control and CDDP-treated mice.
Conclusion:
3Pt is a promising clinical candidate for the treatment of recalcitrant osteosarcoma.
Insights
The novel bone-targeting platinum compound 3Pt demonstrated superior efficacy compared to cisplatinum (CDDP) in inhibiting osteosarcoma tumor growth in a CDDP-resistant mouse model.
Area of Science:
- Oncology
- Pharmacology
- Biomedical Engineering
Background:
- Osteosarcoma is a primary bone cancer with limited treatment options, especially for relapsed or resistant cases.
- Cisplatin (CDDP) is a standard chemotherapy, but resistance is a significant clinical challenge.
- A novel bone-targeting platinum compound, 3Pt, has shown prior inhibitory activity against osteosarcoma.
Purpose of the Study:
- To compare the efficacy of 3Pt with CDDP in a patient-derived orthotopic xenograft (PDOX) mouse model of CDDP-resistant osteosarcoma.
- To evaluate the in vitro and in vivo anti-cancer effects of 3Pt.
Main Methods:
- Established a CDDP-resistant osteosarcoma PDOX model from patient tumor tissue.
- Assessed in vitro osteosarcoma cell viability and calculated IC50 values for 3Pt and CDDP.
- Administered 3Pt and CDDP to PDOX models and monitored tumor growth and body weight.
Main Results:
- 3Pt exhibited a concentration-dependent cytocidal effect in vitro.
- The IC50 value of 3Pt was significantly lower than that of CDDP.
- 3Pt significantly inhibited tumor growth more effectively than CDDP in the PDOX model by day 14.
Conclusions:
- 3Pt demonstrates potent anti-tumor activity against CDDP-resistant osteosarcoma.
- 3Pt represents a promising therapeutic candidate for treating recalcitrant osteosarcoma.
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