Chinese scientists develop peptide drugs to accurately treat prostate cancer

Cancer Cell: Chinese scientists develop peptide drugs to accurately treat prostate cancer

March 26, 2017 - In a new study recently published in the international academic journal Cancer Cell, researchers from the University of Michigan have developed a new treatment strategy that can target approximately half of prostate cancers. Genetic variation.

When the two genes TMPRSS2 and ERG are relocated on the chromosome and fused together, prostate cancer development is initiated. However, the development of small molecule inhibitors targeting ERG has been very challenging.

In this study, the researchers used macromolecular peptides to target ERG, and they demonstrated in cell lines and animal models that this method can effectively target and promote the degradation of ERG fusion proteins, with little impact on normal cell function. .

"Targeting the expression product of this fusion gene is a big challenge. We have solved this problem from another angle," said author Arul M. Chinnaiyan.

The researchers found a group of peptides that specifically interact with ERG proteins. They tested the group on a cell line capable of producing a fusion gene product and found that it could disrupt ERG function. In cells that do not produce this fusion gene product, these polypeptides have little effect on gene expression. They also studied how these peptides affect the biological processes regulated by ERG.

But one of the challenges faced by researchers is that these peptides degrade very quickly and do not last long enough to reach the designated site. Researchers have therefore developed a number of peptide analogs to address the degradation of normal polypeptides, which can last longer.

The researchers also tested these peptide analogs on animal models, and the results showed that these peptide analogs were able to inhibit the growth of prostate tumors that acquired ERG fusion proteins. After prolonged treatment time, more than one-third of mouse tumors showed no signs of recurrence after one month.

"This is a good example of a precise treatment for prostate cancer: only patients with ERG gene fusion are suitable for this drug. ERG fusion proteins are very common in prostate cancer, so these drugs will definitely shine." Chinnaiyan said this.

One drawback of this peptide approach is that such macromolecules cannot pass directly through the cell membrane, which means that these peptides also need to be modified or transported through the cell membrane by some means of transport. Small molecule drugs are favored in drug development because they can easily enter cells and bind to targets.

The researchers will then further analyze the three-dimensional structure of these peptides binding to ERG fusion proteins, hoping to further develop such molecules into small molecules that inhibit ERG. At the same time they will continue to study how to make peptide analogs better.

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