Melanoma Differentiation Associated Gene
Lead Inventors: Paul B. Fisher Ph.D.; Dong-Chul Kang Ph.D.; Rahul V. Gopalkrishnan Ph.D. Problem or Unmet Need:Malignant melanoma is a serious type of skin cancer, due to uncontrolled growth of pigment cells. About 48,000 melanoma related deaths occur worldwide per year. Despite many years of intensive clinical research, the sole effective cure is surgical resection of the primary tumor before it achieves a thickness greater than 1mm. This technology exploited the defective differentiation process in melanoma cancer cells, constructed cDNA libraries from undifferentiated, actively proliferating human melanoma cells and terminal differentiated, growth arrested melanoma cells induced by recombinant human fibroblast interferon (IFN-beta) and mezerein (MEZ). By screening of these cDNA libraries, the technology identifies melanoma differentiation associated gene 5 (mda-5), which is upregulated in terminally differentiating cancer cells by combined treatment with IFN-beta and MEZ, or IFN-beta alone. Further studies showed that mda-5 is an early type I IFN-inducible gene whose expression is elevated in a wide-spectrum of normal and cancer cell types following treatment predominantly with IFN-beta and forced expression of mda-5 in human melanoma cells induces apoptosis. Thereby analyzing mda-5's molecular properties offers potential to obtain insights into the processes of growth control and apoptosis associated with induction of terminal differentiation and irreversible growth arrest in cancer cells.
The differentiation therapy developed by this technology, could efficiently induce terminal differentiation in cancer cells without inducing nonspecific toxicity in normal cells The mda-5 promoter identified by this technology exhibits melanocyte tissue specificity, thereby it can be used to develop melanocytes specific gene therapy with minimized systemic toxicity
The technology developed a novel differentiation therapy, which uses differentiation agents that force cancer cells to resume the process of maturation with a concomitant loss of growth potential The technology provides a method to analyses of gene expression changes in differentiation therapy models, representing a powerful experimental tool for understanding biochemical and molecular events mediating growth arrest of transformed cells The technology identified gene that correlates with and may mediate terminal cell differentiation, representing a novel cancer therapeutic target and a novel diagnostic and screening marker for differentiation therapy
This technology exploited the defective differentiation process in melanoma cancer cells, constructed cDNA libraries from undifferentiated, actively proliferating human melanoma cells and terminal differentiated, growth arrested melanoma cells induce...
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