How pancreatic cancer cells dodge drug treatments – sciencedaily

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Cancer cells can become resistant to adaptation treatments, making them notoriously difficult to defeat and highly fatal. Cold Spring Harbor Laboratory (CSHL) Cancer Center Director David Tuveson and his team investigated the basis of common “adaptive resistance” to pancreatic cancer. They discovered one of the safeguards these cells switch to when faced with cancer drugs.

KRAS is a gene that causes cell division. Most pancreatic cancers have a mutation in the KRAS protein, causing uncontrolled growth. But, drugs that block mutant KRAS do not stop proliferation. Cancer cells find a way to bypass the blockage and continue to divide. Derek Cheng, the study’s lead author and former student of the medical scientist training program in the Tuveson lab, likens this process to back-up engines on a ship. He says:

“You take your main engine off, you’re kind of on back-up engines. But he’s doing fine with those. The ship isn’t sinking yet. It’s still moving at a slower pace. what we want to do is sink the boat. “

Tuveson and his team wanted to understand the “back-up engines” in these cancer cells. They used a technique called biotin proximity tagging to identify which other proteins were interacting with the KRAS mutant. Cheng said, “Basically, I attach a spray can to my favorite protein, or rather my least favorite protein, in this case. And so it attaches biotin, essentially spraying biotin “paint” on neighboring proteins, and we’re able to analyze it to find out which proteins have been tagged. “

Scientists have found “biotin paint” on a protein called RSK1, which is part of a complex that keeps a nearby group of proteins called RAS proteins dormant. Scientists were surprised to find that when they inactivated the KRAS mutant, the neighboring RSK1 complex also stopped working. This allowed the RAS proteins to activate and resume the work of the missing KRAS mutant.

Stopping pancreatic cancer cells may require drugs that can target multiple molecules simultaneously. Tuveson hopes to discover more players that contribute to the adaptation of cancer cells in order to improve future treatments.

Source of the story:

Materials provided by Cold Spring Harbor Laboratory. Original written by Luis Sandoval. Note: Content can be changed for style and length.

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