| References: |
Ombrabulin (AVE8062) hydrochloride is a synthetic derivative of CA-4-P, which inhibits growth in a large number of drug-resistant animal tumors and carcinogen-induced tumors. CA-4-P induces G2/M arrest, thus bringing about cell death by either mitotic catastrophe or apoptosis. Ombrabulin is a vascular disrupting agent.
Target:
Differently from CA-4-P, Ombrabulin does not act directly on the tumor vessels but instead causes constriction of the arterioles, resulting in complete downstream arrest of the blood flow and tumor. Recently, Ombrabulin in combination with cisplatin was used in a phase III clinical trial for patients with advanced soft-tissue sarcomas after failure of anthracycline and ifosfamide chemotherapy, significantly improving progression-free survival. However, this improvement was not clinically relevant, despite being statistically significant. Ombrabulin disrupts the vasculature of established tumours and has shown preclinical synergistic anti-tumour activity when combined with cisplatin. The combination of ombrabulin and cisplatin significantly improved progression-free survival; however, it did not show a sufficient clinical benefit in patients with advanced soft-tissue sarcomas to support its use as a therapeutic option. Predictive biomarkers are needed for the rational clinical development of tumour vascular-disrupting drugs for soft-tissue sarcomas. |
