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NEW YORK DAWN™ > Blog > Health > A brand new druggable most cancers goal: RNA-binding proteins on the cell floor
A brand new druggable most cancers goal: RNA-binding proteins on the cell floor
Health

A brand new druggable most cancers goal: RNA-binding proteins on the cell floor

Last updated: April 23, 2025 9:43 am
Editorial Board Published April 23, 2025
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Credit score: CC0 Public Area

In 2021, analysis led by Ryan Flynn, MD, Ph.D., and his mentor, Nobel laureate Carolyn Bertozzi, Ph.D., opened a brand new chapter in biology, characterizing a brand new type of participant on the cell floor: glycoRNAs. Extending this discovery not too long ago in Cell, Flynn and colleagues confirmed that glycoRNAs kind extremely organized clusters with RNA-binding proteins on the cell floor. These clusters seem to control communication between cells and their setting.

Now, reporting in Nature Biotechnology, Flynn’s workforce within the Stem Cell Program at Boston Kids’s Hospital and Dana-Farber/Boston Kids’s Most cancers and Blood Problems Heart show a primary software of this newfound biology: combating most cancers.

With collaborators on the Cambridge (UK) Stem Cell Institute, led by Konstantinos Tzelepis, Ph.D., and Maria Eleftheriou, Ph.D., they present that one RNA-binding protein on the cell floor, NPM1, may very well be a potent, selective goal for treating acute myeloid leukemia (AML), in addition to strong tumors.

Focusing on the NPM1 protein

AML, a quickly progressive blood most cancers, has been troublesome to focus on therapeutically as a result of a lot of its driving pathways are additionally important for non-cancerous cells, together with blood stem cells.

“The disease may be insensitive to existing drugs, or patients may be too frail to get classical therapeutics, because the toxicity is too high,” says Flynn.

He and his colleagues zeroed in on NPM1 as a result of mutations within the NPM1 gene have been strongly implicated in grownup AML—driving about 60% of instances not attributed to chromosomal abnormalities. Whereas NPM1 is often discovered contained in the cell, Flynn, Tzelepis, and colleagues confirmed that in malignant AML cells, it’s introduced on the floor.

“The amount of cell-surface NPM1 was more than ten times higher on leukemic cells as compared to healthy cells,” says Flynn. “It was very strongly expressed on cells from nearly every patient we looked at. There was more than a 100-fold difference between cancerous and healthy blood stem cells; normal blood stem cells have almost no NPM1 on their surface.”

As a result of it is a floor marker, NPM1 is definitely detectable with easy strategies, and will present a method to monitor sufferers. However the actual great thing about NPM1 being on the cell floor is that it may be readily focused with broadly used brokers equivalent to antibodies.

Utilizing a monoclonal antibody focusing on NPM1, the researchers noticed sturdy anti-tumor exercise in a number of in vivo fashions of AML, whereas noncancerous blood cells and stem cells have been spared. In 4 separate mouse fashions of leukemia, the antibodies neutralized AML and extended survival, with no obvious toxicity.

Most excitingly, the antibodies successfully focused leukemic stem cells in bone marrow samples and mouse fashions.

“This is critical, because a handful of leukemia stem cells can regenerate the cancer even if it appears to be eradicated,” says Flynn.

What about different cancers?

The potential advantages of focusing on NPM1 may prolong to different cancers. The workforce examined 47 human and mouse strong tumor fashions and located that almost all had cell-surface NPM1 to various levels. Experiments in mice advised that monoclonal antibodies focusing on cell-surface NPM1 could be efficient in opposition to sure strong tumors, together with prostate and colorectal most cancers.

“Finding cell-surface targets that are specific to malignancies but spared on healthy tissue has been a long-sought-after goal for immuno-oncology,” says Benson George, MD, Ph.D., within the Flynn Lab, who was co-first creator on the brand new paper with Eleftheriou. “Many cancers lack known molecular handles that can safely be leveraged to signal the immune system to attack. A great example of this is colorectal cancer, which has a rising incidence.”

“The development of novel cancer therapies is largely dependent on the discovery of new cancer biology,” says Konstantinos Tzelepis, collaborator on the Cambridge (UK) Stem Cell Institute. “I am very pleased that our collaborative work has led to the discovery of a promising biotechnology approach to targeting cancers of unmet medical need. Our aim is to better understand and expedite the translation of these novel antigens into new effective treatments.”

In future work, the workforce plans to analyze why cells are bringing NPM1 to the floor, and to discover whether or not clusters of glycoRNA and RNA-binding proteins comprise different targetable molecules related to most cancers.

“We hypothesize that bringing NPM1 to the cell surface is somehow beneficial for the tumor,” Flynn says. “This is really a new class of tumor antigens.”

Extra info:
Jonathan Perr et al, RNA-binding proteins and glycoRNAs kind domains on the cell floor for cell-penetrating peptide entry, Cell (2025). DOI: 10.1016/j.cell.2025.01.040

Remedy of acute myeloid leukemia fashions by focusing on a cell-surface RNA-binding protein, Nature Biotechnology (2025). DOI: 10.1038/s41587-025-02648-2

Supplied by
Kids’s Hospital Boston

Quotation:
A brand new druggable most cancers goal: RNA-binding proteins on the cell floor (2025, April 23)
retrieved 23 April 2025
from https://medicalxpress.com/information/2025-04-druggable-cancer-rna-proteins-cell.html

This doc is topic to copyright. Aside from any truthful dealing for the aim of personal research or analysis, no
half could also be reproduced with out the written permission. The content material is supplied for info functions solely.

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