Novel Drug Shows Potential in Reducing Tumor Growth, Slowing Spread of Liver Cancer

Hepatocellular carcinoma (HCC) accounts for more than 90% of all liver cancers. Because of its limited treatment options and poor prognosis, there is currently an unmet need for alternative, more effective therapies.

In a new study, researchers have developed a novel peptide drug called FFW that could potentially reduce tumor growth and slow progression of the cancer.

Previous studies have examined SALL4, a protein related to tumor growth, as a prognosis marker and drug target for HCC, as well as other cancers. However, it has been previously classified as an “undruggable target,” according to the researchers.

“In our earlier research, we found out that the SALL4 protein works with another protein, NuRD, to form a partnership that is crucial for the development of cancers such as HCC,” Daniel Tenen, PhD, director of the Cancer Institute of Singapore, said in a press release.

Drug molecules that act on protein interactions such as SALL4-NuRD often require the target proteins to have a small “pocket” in their 3D structure in which the drug molecule can reside and take effect, the researchers wrote.

“Instead of looking for ‘pockets’ on SALL4, our research team designed a bio-molecule to block the interaction between SALL4 and NuRD,” Dr Tenen said in the press release. “In our lab experiments, blocking his interaction has led to tumor cell death and reduced movement of tumor cells.”

This bio-molecule, peptide FWW, is a small chain of amino acids that can interfere with these interactions and effectively block the huge protein-protein interaction surface, without needing a “pocket” to take effect. Additionally, the researchers found that FWW could reduce the growth of Sorafenib-resistant HCC, when used in combination with Sorafenib.

Targeting the SALL4-NuRD interaction could have important implications for the treatment of HCC, which could translate to a broader range of cancers with elevated SALL4.

“In our latest work, the research team has also demonstrated an effective strategy to accurately target oncogenes previously considered undruggable,” Dr Tenen concluded in the press release. “Moving forward, we hope to investigate how the targeting of these protein interactions might pan out in other cancer types.”

References

Liu BH, Jobichen C, Chia CS, et al. Targeting cancer addiction for SALL4 by shifting its transcriptome with a pharmacologic peptide. PNAS. 2018. https://doi.org/10.1073/pnas.1801253115

Scientists develop novel drug that could potentially treat liver cancer more effectively [news release]. 2018. https://www.eurekalert.org/pub_releases/2018-08/nuos-sdn080218.php. Accessed August 2, 2018.