Today’s Solutions: February 08, 2023

Cancer is a condition that involves the development of abnormal cells in a certain part of the body that divide uncontrollably, so much so that it can spread to other parts of the body. It is one of the leading causes of death worldwide.

Researchers, medical professionals, and scientists from all across the globe are continually working to come up with preventative treatments and ultimately a cure for this deadly group of diseases. Recently, one method has demonstrated exciting potential. 

Chemist Kevin Shokat from the University of California, San Francisco (UCSF) and his team successfully identified a drug that brings a protein of the cancer-causing KRAS gene (the gene believed to be responsible for a quarter of all tumors) to the cancer cell’s surface. The treatment then transforms the usually inconspicuous protein into a very noticeable “eat me” signal (in the words of the study’s press release) that the body’s immune system can then target.

“The immune system already has the potential to recognize mutated KRAS, but it usually can’t find it very well,” explains co-author Shokat in the release. “When we put this marker on the protein, it becomes much easier for the immune system.”

While the solution of making cancer-causing proteins more detectable to the immune system may sound like a straightforward one, doctors have struggled for years to put it into practice.

This is because even if the KRAS protein can be pinpointed, something that’s already difficult for the body’s immune system because KRAS proteins are normally hiding inside cells, it’s been a challenge to find drugs that can bind to a mutated, cancer-causing KRAS protein’s surface.

What’s so special about ARS1620

Shokat and team turned to the drug ARS1620 in this study, which was published in Cancer Cell. The reason ARS1620 is so significant is that the drug doesn’t just bind to KRAS proteins and block their tumorous effects—it also draws these dangerous proteins to the cell’s surface. Plus, when ARS1620 binds to KRAS proteins, they form an alert to the body’s immune system that tells it to destroy the cell they’re on.

“This mutated protein is usually flying under the radar because it’s so similar to the healthy protein,” says another one of the study’s authors Charles Craik, a professor of pharmaceutical chemistry at UCSF. “But when you attach this drug to it, it gets spotted right away.”

The researchers explain that through ARS1620 they were able to come up with a new form of immunotherapy that activates the immune system to recognize and target cancerous KRAS. The drug even worked on KRAS cells that were already resistant to the drug.

The treatment is yet to be tested on humans.

Source study: Cancer Cell—A covalent inhibitor of K-Ras(G12C) induces MHC class I presentation of ha-tenanted peptide neoepitopes targetable by immunotherapy

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