Researchers at the University of Rochester have developed a new method for cutting off cancer's ability to proliferate. The technique works by blocking certain proteins that cancer cells use to trigger uncontrolled growth in neighboring healthy cells, and it could lead to a new kind of treatment that cancer can't develop a resistance to.

Proteins use the hedgehog signaling pathway to stimulate cells to grow and spread, so it's particularly active while humans (and all mammals) are developing in the womb. By the time an animal reaches adulthood, however, the pathway mostly lies dormant and is only active in those cells that are constantly regenerating, like our skin.

But some types of cancer proliferate by hijacking this largely abandoned pathway. Cancer cells produce certain ligands, molecules that bind to receptors on the surface of nearby healthy cells. That leads the healthy cells to release growth molecules, which causes a runaway effect of unregulated cell growth. In turn, that increases the amount of cancerous cells and the cycle continues exponentially.

Recognizing this, the Rochester team developed a method to block the hedgehog signaling pathway. The researchers developed a cyclic peptide that effectively forms a shield around healthy cells, preventing the cancer's protein messengers from getting inside and triggering the release of growth molecules.

The Rochester researchers aren't the first to single out the hedgehog pathway as a possible cancer treatment target. Back in 2012, the US Food and Drug Administration approved a drug called Vismodegib, which cuts off the cancer cells' ability to send the signaling proteins. Unfortunately, more recent studies suggest that cancer cells can quickly become resistant to the drug.

The difference here is that the cyclic peptides target the healthy cells, not the cancerous ones. By interrupting the pathway at the receiving end instead of on the cancer cells themselves, cancer isn't likely to be able to develop a resistance to the treatment.

"It is important to have different weapons against this pathway, and we have targeted a key component of it," says Rudi Fasan, lead researcher on the project.

That said, there is still the risk that the treatment will also affect healthy cells that still rely on the same pathway, such as those in the skin, blood vessels and digestive tract. The researchers say that the potential benefits likely outweigh the risks, but these won't be fully known until the drug goes to human trials. For now, the team is working on optimizing the peptide to boost its effectiveness, before they move onto animal trials.

The research was published in the Journal of the American Chemical Society.

Source: University of Rochester

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