Repurposing Romidepsin for Osteosarcoma: Screening FDA-Approved Oncology Drugs with Three-Dimensional Osteosarcoma...

Area of Science:

• Oncology
• Pharmacology
• Biotechnology

Background:

• Osteosarcoma is the most common primary malignant bone tumor, with poor survival rates, especially when lung metastases are present.
• Existing therapies have limited efficacy against micrometastases, necessitating novel treatment strategies.
• Targeting the growth of lung micrometastases is crucial for improving patient outcomes in osteosarcoma.

Purpose of the Study:

• To screen FDA-approved oncology drugs for efficacy against highly metastatic human osteosarcoma cell lines.
• To identify novel therapeutic agents capable of inhibiting the growth of osteosarcoma micrometastases.
• To evaluate romidepsin as a potential repurposed drug for osteosarcoma treatment.

Main Methods:

• A 3D multicellular in vitro osteosarcoma spheroid (sarcosphere) model was utilized to simulate in vivo micrometastases.
• An NCI panel of FDA-approved oncology drugs was screened using three highly metastatic human osteosarcoma cell lines.
• Romidepsin's efficacy was assessed based on sarcosphere viability, both alone and in combination with standard chemotherapeutics (MAP).

Main Results:

• Romidepsin was identified as the most promising inhibitor among 13 initial hits, demonstrating potent anti-cancer activity in sarcosphere viability assays.
• The drug showed efficacy at clinically achievable concentrations without affecting non-transformed cells and outperformed other histone deacetylase inhibitors.
• Sarcospheres from human and canine patient samples exhibited sensitivity to romidepsin, indicating its potential clinical relevance.

Conclusions:

• Romidepsin is a promising candidate for repurposing in the treatment of metastatic osteosarcoma in both human and canine patients.
• The sarcosphere-based screening approach effectively identified romidepsin-sensitive and -resistant patient populations.
• This screening strategy may aid in stratifying patients likely to respond to romidepsin or other therapeutic agents.