Researcher discovers key gene responsible for cancer drug resistance
Findings may represent opportunity to enhance effectiveness of drug
therapy

Date:
October 12, 2021
Source:
University of Missouri-Columbia
Summary:
A researcher has discovered an enzyme that plays a key role in
the ability of cancer cells to resist drug treatment.



FULL STORY ==========================================================================
A researcher at the University of Missouri School of Medicine has
discovered an enzyme that plays a key role in the ability of cancer
cells to resist drug treatment.


========================================================================== Immunomodulatory drugs like thalidomide, lenalidomide and pomalidomide
have improved the treatment of patients with multiple myeloma and other
blood cancers. But almost all patients eventually develop resistance to
these therapies.

Principal investigator Thang Van Nguyen, DVM, PhD, an assistant research professor in the Center for Precision Medicine, discovered that a protein called USP15 is highly expressed in cancer cells that become resistant
to the standard immunomodulatory drugs.

"This USP15 protein protects the cancer cells from destruction by
removing ubiquitin tags placed on the cells by the immunomodulatory
drugs," Nguyen said.

"Those tags initiate the cell degradation process. But if those tags are removed by USP15, the cancer cells will continue to grow and multiply."
Nguyen believes testing multiple myeloma patients for USP15 will
help determine if a patient will be resistant to immunomodulatory
drug therapy. That knowledge could lead to a more precise, customized treatment.

"This work could lead us to discover whether a USP15 inhibitor in
combination with other drugs will be more effective to treat cancers,"
Nguyen said.

"Further studies will be required to determine the best combination to
improve clinical outcomes of patients with multiple myeloma and other
types of cancer." Nguyen's study, "USP15 antagonizes CRL4CRBNa-mediated ubiquitylation of glutamine synthetase and neo-substrates," was published
in the journal Proceedings of the National Academy of Sciences of the
United States of America.

Nguyen declares he has no conflicts of interest.

========================================================================== Story Source: Materials provided by University_of_Missouri-Columbia. Note: Content may be edited for style and length.


========================================================================== Journal Reference:
1. Thang Van Nguyen. USP15 antagonizes CRL4CRBN-mediated ubiquitylation
of
glutamine synthetase and neosubstrates. Proceedings of the National
Academy of Sciences, 2021; 118 (40): e2111391118 DOI: 10.1073/
pnas.2111391118 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/10/211012102700.htm

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