A research team at the Cancer Research Institute (CSI) of the National University of Singapore has developed a novel peptide drug called FFW that may prevent the development of hepatocellular carcinoma (HCC) or primary liver cancer . This landmark discovery opens the door for more effective treatment of liver cancer and reduced side effects.
SALL4 is a protein associated with tumor growth and has been used as a prognostic marker and drug target for HCC, lung cancer and leukemia. It is usually present in a growing fetus, but is inactive in adult tissues. In some cancers, such as HCC, SALL4 is reactivated, leading to tumor growth.
Drug molecules that act on proteins, such as SALL4-NuRD, usually require the target protein to have a small “pocket” in its 3-D structure, where the drug molecules can exist and function. In the early research, it was found that the SALL4 protein interacts with another protein NuRD, forming a partnership that is crucial for the development of cancers such as HCC. SALL4 designed by this research team did not look for ‘pockets’, but designed biomolecules that block the interaction between SALL4 and NuRD. Studies have found that blocking this interaction can cause tumor cell death and reduce tumor cell movement.
FFW can effectively block protein-protein interactions, and does not require “pockets” to take effect. The research team also found that when combined with sorafenib, FFW can reduce the growth of sorafenib-resistant HCC. Although most targeted therapies are small-molecule drugs, well-designed peptide drugs (such as FFW) tend to have higher selectivity than large-molecule surfaces and are less toxic than small molecules.
Singapore researcher Dr. Liu Bee Hui said: Based on the information we have obtained from the structure and global gene expression, we continue to study this peptide and other peptides with similar structures in order to eventually make them clinical grade drugs and bring patients benefit.
