Promising New Research on Prostate Cancer

(CN) — A class of manmade molecules that function like antibodies can kill prostate cancer tumors in mice without hurting healthy tissue, the National Academy of Sciences reported Monday.

The findings in the journal Proceedings of the National Academy of Sciences suggest that aptamers could form the basis of new cancer therapies if future human and animal trials are successful.

Aptamers are peptide (amino acid chains) or oligonucleotide molecules that bind to a target molecule.

“The benefit of aptamers compared to antibodies is that we have more control over where they go and what they do,” said senior author Bruce Sullenger, a professor at Duke University. “In our study, we also developed an antidote that shuts down the aptamer almost immediately, and this is an advantage if, for whatever reason, there might be an adverse reaction.”

Aptamers can be produced to target cancer cells, similar to the way the body’s naturally generated antibodies home in on pathogens such as bacteria or viruses. Recent drug advances have combined antibodies with chemotherapy to create immunotherapies that successfully battle cancer.

However, inflammation and other side effects are common in these drug combinations because it is difficult to control where and how strongly the antibodies trigger immune responses beyond cancer cells.

“A need exists for new tumor-targeting therapies that are easier to manipulate and synthesize,” said co-author Linsley Kelly, a postdoctoral researcher at Duke.

Researchers are studying aptamers as promising alternatives. They are produced using single RNA or DNA strands, which have the same targeting capability as antibodies, but appear to be nontoxic.

For the study, the team focused on an RNA ligand — a molecule that binds to another, typically larger, molecule — called E3, which selectively targets prostate cancer cells. They added the E3 aptamer to a small dose of a highly toxic chemotherapy agent, injecting the drug combination in mice that have human prostate cancer tumors.

The mice lived up to 74 days, compared to 46 days for mice that were not given the treatment.

The researchers also developed an antidote to block toxicity from the E3 aptamer-drug combination, which acts as a safety switch in the unexpected event of normal cells being killed.

“That was one of the really exciting things from this work,” said lead author Bethany Powell Gray, a senior research associate at Duke. “Because they are single strands of RNA, they can be reversed by using a complementary portion of RNA that will bind and make a double strand to unfold the aptamer.”

The team said animal studies focusing on other types of cancer will continue.

“This study demonstrates that E3 RNA selectively internalizes into prostate cancer cells and that E3-highly toxic drug conjugates are potent anti-tumor agents, representing a potential new therapeutic approach,” Sullenger said.

The research was funded by the Department of Defense Prostate Cancer Research Program Post-Doctoral Training Award, the Synergistic Idea Award, Stand Up to Cancer Innovative Research Grant, and National Cancer Institute grants.

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