New insights into melanoma development and therapy
Source: Eurek Alert!, September 2023
Osaka, Japan – Malignant melanoma is a type of skin cancer that originates from melanocytes or nevi, causing about 80% of skin cancer-related deaths. While some cases have shown significant response to existing molecular targeted therapies, as well as immune checkpoint inhibitors, there are also instances in which these treatments have proven ineffective. Therefore, the development of new therapeutic agents for cases resistant to these drug therapies has been required.
In a study published this month in Oncogene, researchers from Osaka University have discovered that the expression of a specific isoform of GREB1 isoform 4 (Is4) is induced in malignant melanoma cells under the influence of the melanocyte-specific transcription factor, MITF and GREB1 Is4 promotes cancer cell proliferation and the regulation of pyrimidine metabolism. Furthermore, the anti-tumor effect of antisense nucleic acids against GREB1 showed a potential new modality for malignant melanoma.
To investigate the mechanisms by which GREB1 Is4 is induced in malignant melanoma and involved in its growth, the research group used a mouse model of malignant melanoma and human clinical samples to comprehensively demonstrate that induction of GREB1 Is4 expression by the MITF transcription factor is important in malignant melanoma development and prognosis.