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ERBB4 Mutations Mutation Identified in Human Melanoma Metastasis Cell Lines (2690, 2379, 2197, 2183, 2535, 2645, 1770, 2359, 223

Posted Nov 25 2010 7:00pm

Description of Invention:
Protein tyrosine kinases (PTKs) have been associated with a wide variety of cancers, including melanoma. Using high-throughput gene sequencing, the NIH has analyzed PTKs in melanoma and identified several novel somatic alterations, including alterations in ERBB4 (also called HER4). These mutations were found to increase the sensitivity of cells in which they reside to small molecule inhibitors, such as lapatinib.

Available for licensing are several melanoma cell lines that harbor ERBB4 mutations. These cell lines provide methods of identifying specific inhibitors to ERBB4 that could be used to treat patients with ERBB4 mutations as well as methods to further understand the role of ERBB4 mutations in melanoma. Given the recent success of small molecule protein kinase inhibitors and specifically inhibitors to epidermal growth factor receptor (EGFR) (such as gefinitib and erlotinib), these reagents could be used to further the development of specific inhibitors to ERBB4 and improve existing melanoma treatments for patients with these mutations.

Applications:
  • In vitro and in vivo cell model for understanding the biology of ERBB4, including growth, motility, invasion, and metabolite production.
  • High throughput drug screening to test for ERBB4 inhibitors that could be used to treat particular cancers, such as melanoma.
  • Diagnostic array for the detection of ERBB4 mutations.
  • Research tool to generate cell lines where the ERBB4 mutation is knocked out or the wild type gene is knocked in using an adeno-associated virus. These resulting cells can be used understand the underlying biology of ERBB4 phenotypes or to identify candidate small molecule and other therapeutic drugs.


Advantages:
  • Cell lines are derived from melanoma patients: These cell lines are likely to retain many features of primary melanoma samples. For example novel melanoma antigens identified from this cell line would be expected to correlate with antigens expressed on human melanoma tumors. Studies performed using these cell lines could be used to elucidate the biological basis of initiation and progression of melanoma in humans as well as aid in the identification and/or testing of ERBB4 inhibitors.
  • Expresses the ERBB4 mutation in melanoma: ERBB4 is a highly mutated gene in melanoma, suggesting its important functional role in the disease. Therefore, these cell lines represent a tool that can be utilized to study the impact of the ERBB4 gene and the associated mutations on melanoma, and possible other cancers since mutations in ERBB family members such as EGRF and ERBB2 are prevalent in lung cancer, glioblastoma and gastric cancer.


Inventors:
No Inventor Information Available.

Patent Status:
Research Tool. Patent protection is not being pursued for this technology.

Licensing Status:
Available for licensing

Collaborative Research Opportunity:
The National Human Genome Research Institute’s Cancer Genetics Branch is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate and/or commercialize these newly characterized ERBB4 mutant cell lines as well as to identify and test ERBB4 inhibitors as possible therapeutic drug candidates to treat melanoma and other cancers. Please contact Dr. Yardena Samuels at samuelsy@mail.nih.gov for more information.


For Licensing Information Please Contact:
Whitney Hastings
NIH Office of Technology Transfer
6011 Executive Blvd. Suite 325,
Rockville, MD 20852
United States
Email: hastingw@mail.nih.gov
Phone: 301-451-7337
Fax: 301-402-0220


Ref No: 2194

Updated: 11/2010

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