Dr. Park on Alisertib in Myc-Overexpressing Lymphoma Cells

Steven I. Park, MD, director, Lymphoma Program, associate professor of Medicine, Leukemia, Lymphoma, and Myeloma Program, University of North Carolina (UNC) at Chapel Hill, Lineberger Comprehensive Cancer Center, Clinical Research, discusses how alisertib induces synthetic lethality and overcomes chemoresistance in Myc-overexpressing lymphoma cells.

Because Myc has been proven to be difficult to directly target, UNC researchers examined several Myc-expressing pathways, Park explains. A preclinical study investigated the aurora kinase inhibitor alisertib—which has shown promise in solid tumors as well as T-cell lymphoma—in Myc-overexpressing lymphoma cells that are resistant to conventional chemotherapy agents.

When combined with cyclophosphamide, alisertib induced apoptosis and cell cycle arrest of Myc-overexpressing tumor cells. In xenograft models, the combination was also shown to overcome chemoresistance, induce complete regression of tumors, and improve overall survival. This will be studied further in a clinical trial, Park adds.