Not all cancer drugs work in patients with the fatal disease.
The research findings from the University of Otago shed a lot of light on why new immunological checkpoint inhibitor therapies such as nivolumab and pembrolizumab were approved by the New Zealand Government for the first time in 2016 to treat metastatic melanoma, It does not work in many patients.
The new immunotherapeutic drugs herald a significant breakthrough in the cure of cancer. But while they may be effective for some patients with melanoma, for others the therapies do not work at all, and most eventually become resistant to immunotherapy treatments.
One of the key components of the immune control mechanism is a protein on the surface of cancer cells called PD-L1 that can potentially be receptive or block immunotherapy.
The researchers were able to demonstrate that epigenetic modification – DNA modifications that do not directly alter the DNA sequence, but change the frequency with which a cell uses specific genes, specifically DNA methylation, influences whether PD-L1 is expresses on the surface of the cancer cell.
"Currently, there are no reliable biomarkers to predict the benefit of immune therapy in melanoma and these are desperately needed in the clinic." said an investigator Chris Jackson.
Jackson added that biomarkers help choose patients who will probably benefit and those who do not.
"Many groups around the world are looking for biomarkers of immune therapy and this Otago discovery of an epigenetic marker seems very promising," he added.
Jackson believes that the findings will now have to be tested on people with melanoma undergoing treatment to see if this test can do so "from the bench to the bedside."
Another principal investigator, Aniruddha Chatterjee, says the findings suggest that epigenetic therapies could be used in clinical trials in combination with melanoma immunotherapy to treat patients. However, additional trials would be needed before this could become a possibility.
Due to the lack of availability of solid biomarkers, it is difficult to predict a patient's response and also a relatively minor understanding based on resistance to melanoma immunotherapy treatment.
There is a global effort to uncover the secrets behind resistance to immunotherapy and Otago researchers believe they may have discovered a key piece of the puzzle.
DNA methylation is an epigenetic mechanism that plays a key role in changing genes "on" or "off" and helps determine cell function. In general, DNA methylation silences gene expression and has been implicated in cancer.
"Our research provides evidence that it is the overall loss of DNA methylation that regulates the constitutive expression of the PD-L1 immune control point in melanoma," said Chatterjee.  The findings have been announced internationally by their colleagues as "highly innovative" and a major advance in understanding the biology of melanoma.
The study appears in the iScience journal.
(This story has not been edited by Personal Business Standard and is self-generated from a syndicated feed)