In this section from a fibrolamellar carcinoma tumor, bright points indicate interactions between two proteins that are not seen in normal tissue. Image credit: Turnham, Smith et al. (CC BY 4.0)
Fibrolamellar carcinoma (or FLC for short) is a rare type of liver cancer that affects teenagers and young adults. FLC tumors are often resistant to standard radiotherapy or chemotherapy treatments. The only way to treat FLC is to remove tumors by surgery. However, often the tumors come back after initial treatment and spread to other locations. Therefore, there is a genuine need to improve the treatment options available to FLC patients.
The tumor cells of FLC patients contain a genetic defect that fuses together two genes, which produce proteins called DNAJ and PKAc. Normally, DNAJ helps other proteins in the cell to fold into their correct shapes, while PKAc is an enzyme that can control how cells communicate. However, it is not clear what the abnormal DNAJ-PKAc fusion protein does, or how it causes FLC.
Turnham, Smith et al. have now used gene editing to make mouse liver cells that mimic the human FLC mutation. Biochemical experiments on these cells showed that the DNAJ-PKAc protein brings together unique combinations of enzymes that drive uncontrolled cell growth. Analyzing cells taken from tumors in FLC patients confirmed that these enzymes are also activated in the human disease. Turnham, Smith et al. also found that combinations of drugs that simultaneously target the DNAJ-PKAc protein and the recruited enzymes slowed down the growth of FLC cells. More experiments are now needed to test these drug combinations on human FLC cells or in mice.
