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New molecular information may help develop more effective treatments for melanoma

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New research reveals important molecular information that may help scientists develop more effective treatment and prevention strategies for difficult-to-treat forms of melanoma skin cancer.

In this new report, researchers at The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solab Institute (OSUCCC – James) account for 15-20% of all major genetic mutations. The features are specified and explained. melanoma..

Using a preclinical test model, the team is specific NRAS Gene mutations that occur in human melanoma are directly related to the ability of the gene mutation to initiate spontaneous melanoma formation.

“This means that the characteristics of the mutant itself are responsible for cancer formation, rather than being prone to specific genetic mutations,” said Corresponding, Associate Professor of Molecular Genetics at Ohio State University. The author, Christine Bird, states. Art Science, Department of Molecular Genetics, OSUCCC – Member of James Molecular Cancer Development and Chemistry Prevention Program.

NRAS mutant cancer is difficult to treat because there is no effective treatment other than immunotherapy. Each cancer type seems to prefer a particular “flavor” of the mutant NRAS, and it is not clear why this is... “


Christin Burd, Ohio State University Faculty of Arts and Sciences Research Response Author and Associate Professor of Molecular Genetics

OSUCCC-James wanted to know what caused melanoma NRAS Mutants that are different from mutants that promote other types of cancer. Scientists say this knowledge may help researchers identify the early events required for melanoma formation and develop treatments to prevent melanoma.

Burd and colleagues in the June 7, 2022 issue Nature Communications..

Study design and method

To carry out this study, OSUCCC-James researchers have developed a genetically engineered model that allows activation of one of nine different models. NRAS-Mutations in melanocytes, which are pigment cells that form melanoma.

“Surprisingly, when these gene mutations were activated, only those found in human disease developed melanoma,” Bird said. “Some mutants did not cause melanoma, but they are known to cause leukemia. This finding is NRAS Mutations are unique to each tumor type and occur during the development of the cancer rather than responding to specific mutagenic events such as exposure to sunlight. “

In collaboration with Sharon Campbell, a structural biologist at the University of North Carolina (UNC) Chapel Hill, and Debbie Morrison at the National Institutes of Health, Bird’s team NRAS Mutants capable of initiating melanoma that allow these proteins to better interact with signaling pathways that promote melanoma growth.

“Now we will work to target this unique structural feature of N, which induces melanoma.RAS A variant to prevent and / or treat the disease, “Bird said. Such concepts can be used to find vulnerabilities in other RAS-driven tumor types. “

To facilitate similar discoveries, the team has generated eight new publicly available genetically engineered mouse models that serve as an essential toolkit for the entire RAS community. Burd states that these models can be used to activate and study the role of NRAS. It is a type of other related cancer such as colon cancer, leukemia, myeloma, thyroid cancer. They can also be used to investigate new drugs for these diseases.

sauce:

Journal reference:

Murphy, BM, et al.. (2022) Enhanced BRAF involvement by NRAS mutants capable of promoting the onset of melanoma. Nature Communications.. doi.org/10.1038/s41467-022-30881-9

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