Researchers from University of Otago identified mechanism behind frail success rate of new cancer therapies in several patients against metastatic melanoma.
The research led by Dr. Aniruddha Chatterjee, senior research fellow in the Department of Pathology at University of Otago, along with Professor Mike Eccles and Professor Peter Hersey from the University of Sydney reveled that therapies such as nivolumab and pembrolizumab are inefficient against metastatic melanoma. These immunotherapeutic drugs showed inconsistence in curing melanoma in some patients as they become resistant to immunotherapy treatments. The team showed that DNA modifications changed the frequency of the usage of specific genes by the cell without altering the DNA sequence. The researchers identified such trails in DNA methylation, which is an epigenetic signaling tool that can play a major role in switching genes on or off. PD-L1 is a protein on the surface of cancer cells that is an important part of the immune checkpoint mechanism, which can potentially be receptive to or block immunotherapy. The researchers state that there are no biomarkers reliable enough to predict benefits from immune therapy in melanoma. Moreover, biomarkers would identify the cases that benefit from the therapy. The researchers believe that DNA methylation can restrict gene expression to help determine cellular function. The global loss of DNA methylation regulates constitutive expression of the immune checkpoint PD-L1 in melanoma. The research was published in the online journal iScience on June 29, 2018.
The research can be beneficial in applying epigenetic therapies in clinical trials along with immunotherapy in melanoma to treat patients. The Health Research Council awarded $1,198,714 to the researchers to boost their work in developing a DNA methylation marker panel to predict cases of melanoma responding to immunotherapy treatment.