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CMCC 1779

Treatment and Diagnostic for Melanomas

Inventors: Leonard Zon, Craig Ceol, Yariv Houvras

Invention Types: Diagnostic/Prognostic, Therapeutics

Research Areas: Oncology/Hematology

Keywords: Animal Model (zebra fish), Biomarker

For More Information Contact:  Wong, Adrienne

 

Invention Description:

Melanoma is an aggressive malignancy which often first presents with advanced metastasis and for which treatment options are limited. In an effort to identify novel targets for the treatment of melanoma, Dr. Zon's lab has designed and performed a screen using a zebrafish model system of melanoma induced by the oncogenic BRAF-V600E mutation and deficiency for the p53 tumor suppressor, mutations which are commonly seen in human melanomas. Screening for genes capable of enhancing the generation of melanoma, the lab identified the SETDB1 gene, encoding a histone-lysine N-methyltransferase responsible for trimethylation of lysine 9 on histone H3, a specific tag for epigenetic transcriptional repression.

Since the human SETDB1 gene is within a chromosomal region known to be amplified in human melanoma, this finding may provides a marker for melanoma diagnostics and a prognostic marker useful for identifying a subset of melanomas which have a more aggressive clinical course. Further, the studies indicate that overexpression of SETDB1 leads to more aggressive melanomas with enhanced local invasiveness. This suggests that SETDB1 may be an attractive target for therapeutics in treating human melanoma and other malignancies with BRAF-V600E mutations or other Ras pathway overactivation.

Applications:

• Zebrafish models for screening drug candidates
• Diagnostic and prognostic test for melanoma
• Therapeutic target

Competitive Advantages:

Currently, there limited therapies for melanoma and other aggressively metastatic cancers. This technology provides an attractive in vivo screening model for melanoma therapies targeting SETDB1 histone methyltransferase.

Business Opportunity:

• Exclusive or non-exclusive license to a company

Key Publications: Ceol CJ, Houvras Y, Jane-Valbuena J, et al. The histone methyltransferase SETDB1 is recurrently amplified in melanoma and accelerates its onset. Nature. 2011 Mar 24;471(7339):513-7.

Related Publications: Tan JL, Fogley RD, Flynn, RA, et al. Stress from nucleotide depletion activates the transcriptional regulator HEXIM1 to suppress melanoma. Mol Cell. 2017 Apr 7;62(1):34-46.

Pat. US 9,040,286 B2

IPStatus: Pat. Pend.