In a recent study funded by FCF, scientists at Fred Hutch Cancer Center in Seattle, Washington outlined the potential importance of Polo-like kinase 1 (PLK1) as a promising therapeutic target in FLC. The paper, DNAJ-PKAc fusion heightens PLK1 inhibitor sensitivity in fibrolamellar carcinoma, was published on April 24 in the journal Gut. The effort was led by Taran Gujral, PhD, Associate Professor in the Human Biology Division.

Fred Hutch wrote a news story summarizing the study’s findings (“Rare cancer researchers find promising target in fibrolamellar cancer“). In addition to Dr. Gujral, the article features comments from researchers and patients in the fibrolamellar community, including

• Kim Riehle, MD, FACS, a surgeon at Seattle Children’s Hospital
• John Scott, PhD, Professor and Chair of Pharmacology at the University of Washington
• David Burch, a FLC patient who shared his perspectives on the disease and the importance of ongoing research efforts.

While it is known that FLC is driven by a fusion protein (DNAJ-PKAc), specifically how that protein causes tumor growth is not fully understood. To help answer that question, this study investigated other kinases, proteins that are often involved in cell growth, migration and proliferation. It found that:

• Polo-like kinase 1 (PLK1) is important to fibrolamellar carcinoma (FLC) cell survival
• Within a cell, the fusion protein that drives FLC localises to the centrosome (an organelle involved in cell division) where it interacts with PLK1
• The inhibition of PLK1 genetically or with drugs significantly reduced FLC cell growth
• PLK1 inhibitors (currently in early clinical trials) effectively suppressed tumor growth in multiple fibrolamellar models, suggesting that there is strong potential for PLK1-targeting therapies in FLC.

This work lays the groundwork for potential clinical studies of PLK1 inhibition in FLC, possibly in combination with other drugs.

Please click here to read or download the published study.