Avanish Vellanki, Cofounder and CEO at Rain Therapeutics, describes the mechanism of action of milademetan (RAIN-32), an investigational MDM2 inhibitor which is currently being studied as a treatment for dedifferentiated liposarcoma in a phase 3 clinical trial.
Liposarcoma is a rare cancer originating from fat cells located in the soft tissues of the body. It is a malignant cancer that can spread to other parts of the body. Well-differentiated liposarcoma is less aggressive and tends to present as a large painless mass found in deeper tissues. Dedifferentiated liposarcoma is more aggressive, arising from well-differentiated liposarcoma, and is usually found in tissue behind the abdominal area or the extremities. Well-differentiated and dedifferentiated liposarcoma are the most frequent subtypes of liposarcoma and share common genomic abnormalities, predominately MDM2 gene amplification.
As Mr. Vellanki explains, MDM2 plays a crucial role in the regulation of tumor protein 53 (p53). P52 controls the cell cycle and is, thus, critical for tumor suppression. When MDM2 is overexpressed, p53 can be inactivated, which can result in tumor growth and disease progression for cancer patients. Milademetan inhibits MDM2, and, in doing so, is hypothesized to reactivate p53.
To learn more about MANTRA, the phase 3 clinical trial in which milademetan is being compared to standard of care in dedifferentiated liposarcoma patients, go here (link Vellanki clinical trial article).
To learn more about dedifferentiated liposarcoma and other rare cancers, visit checkrare.com/diseases/cancers/