A Peptide That Protects Against Liver Cancer

Scientists in Singapore have developed a peptide drug that interferes with a molecular interaction that drives liver cancer progression.

AsianScientist (Aug. 16, 2018) – A research team led by scientists from the Cancer Institute of Singapore (CSI Singapore) has developed a peptide drug that could potentially stop the development of hepatocellular carcinoma (HCC). Their findings are published in the Proceedings of the National Academy of Sciences.

HCC is a fast-growing cancer of the liver, and patients typically survive 11 months after diagnosis. HCC accounts for over 90 percent of all liver cancers and poses a major public health problem in the Asia Pacific region.

The main first-line treatment for HCC is the drug Sorafenib, which has adverse side effects and prolongs survival for only three months. The lack of effective treatment alternatives, coupled with late discovery, has led to HCC becoming the second leading cause of cancer deaths worldwide.

In the present study, scientists in Singapore developed a peptide that targets SALL4—a protein related to tumor growth which was previously classified as an ‘undruggable target’.

“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. Instead of looking for ‘pockets’ on SALL4, our research team designed a biomolecule to block the interaction between SALL4 and NuRD. In our lab experiments, blocking this interaction has led to tumor cell death and reduced movement of tumor cells,” explained Professor Daniel Tenen, director of CSI Singapore.

The peptide, which the research team called FFW, is a small chain of amino acids that can interfere with SALL4-NuRD interactions. The scientists demonstrated that when used in combination with Sorafenib, FFW could reduce the growth of Sorafenib-resistant HCC. While most targeted therapies are small molecule drugs, a well-designed peptide drug, such as FFW, tends to possess higher selectivity over large binding surfaces and exhibit a safer toxicity profile than small molecule drugs.

“Based on the information we gained from structural and global gene expression, we are continuing our work on this peptide and other peptides with similar structures, with the aim of eventually being able to make them into clinical grade drugs for the benefit of patients,” said Dr. Liu Bee Hui, a research fellow at CSI Singapore who is the first author of the study.

“Moving forward, we hope to investigate how the targeting of these protein interactions might pan out in other cancer types,” Tenen added.

The article can be found at: Liu et al. (2018) Targeting Cancer Addiction for SALL4 by Shifting Its Transcriptome With a Pharmacologic Peptide.


Source: National University of Singapore; Photo: Shutterstock.
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