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Science warns: Luminous tumor markers may interfere with cancer research, causing reproducibility problems

 Last Update: 2022-03-02
 Source: Internet
 Author: User

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Cancer biologist Cyrus Ghajar was preparing to study how the immune system fights breast cancer when he encountered a conundrum: The cancer cells he implanted in mice, which he said had spread rapidly, stayed the same, sometimes disappearing after about 11 days

Then, postdoc Candice Grzelak found the culprit: green fluorescent protein (GFP), which the researchers use to track cells

But he and others say the lab's experience reflects a broader question in mouse studies of immunotherapy, a powerful therapy that harnesses the immune system to defeat tumors: the glowing proteins that biologists use to track cancer cells, usually from fireflies Or borrowed from jellyfish, and may be sparking their own immune attack on cells

This phenomenon may explain why laboratories sometimesCannot replicate immunotherapy results in other groupsGlenn merlino, a cancer biologist at the National Cancer Institute (NCI), advises

"So many preclinical experiments don't tell you anything clinically useful," Merlino said

That's because most labs use mice that lack immune systems so they don't reject the transplanted human cancer cells that are often used to evaluate treatments

Ghajar and others transferred into mouse cancer cells, but the cells were not immediately rejected

They lowered GFP levels, but the cancer cells still didn't metastasize

In their review, Merlino and his NCI co-authors warn that the same problematic immune response could arise using other light-emitting proteins from different species, the viral proteins that cause cancer, and even the DNA-cutting enzyme Cas9 from CRISPR from bacteria in the experiment

Researchers may need to find solutions, such as modifying mouse strains to tolerate foreign proteins, like the mice in Ghajar's lab

The researchers point to other causes of replication problems in cancer biology, such asVariation in the mouse microbiome

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