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The research results of the University of Otago do not help to understand why new anti-checkpoint immune therapies like nivolumab and pembrolizumab have been approved by the New Zealand government. for the first time in 2016 to treat metastatic melanoma does not work on many patients.
The new immunotherapeutic drugs announce a significant advance in the treatment of cancer. Although they may be effective in some patients with melanoma, in others, the therapies do not work at all and most eventually become resistant to immunotherapy treatments.
One of the main components of the immune mechanism is a protein on the surface of the skin. cancerous cells called PD-L1 that can potentially be receptive or block immunotherapy.
The researchers were able to show that epigenetic modification – changes in DNA that do not directly alter the DNA sequence but change the frequency of use of a gene. Cell Specific genes – specifically the methylation of DNA, influence the expression of PD-L1 on the surface of cancer cells.
"Currently, there is no reliable biomarker to predict the benefits of immunotherapy in melanoma. said researcher Chris Jackson.
Jackson added that biomarkers help to select which patients are eligible and who are not.
"Many groups around the world are s Otago's discovery of an epigenetic marker looks very promising," he adds.
Jackson think the results will now have to be tested in people with melanoma being treated to see if this test can do it. "
Another lead researcher, Aniruddha Chatterjee, says the findings suggest that epigenetic therapies could be used in clinical trials in combination with immunotherapy in melanoma to treat patients.However, further trials would be needed before this becomes a possibility
Unavailability of robust biomarkers makes it difficult to predict a patient's response and also a relatively lesser understanding of resistance to immunologic treatment of melanoma.
Otago researchers believe that they have discovered a key piece of the puzzle
The methylation of DNA is an epigenetic mechanism that plays a key role in the change genes "on" or "off" and helps determine cellular function. "Our research provides evidence that this is the overall loss of DNA methylation that regulates the constitutive expression of the PD-L1 immune control point in melanoma," Chatterjee said. 19659002] Findings have been announced by international research peers as "highly innovative" and a major breakthrough in understanding the biology of melanoma.
The study appears in the journal iScience.
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