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Researchers investigate why some skin cancers stop responding to therapy at end of life

Changes in the order, structure, and number of copies of tumour DNA could be the reason some skin cancers ultimately resist treatment, according to research from the Francis Crick Institute, University College London and The Royal Marsden in London.

The research was part of the PEACE study, funded by Cancer Research UK, which analyzed tumour samples from people who died from melanoma. They hope this new information about the resistance of some melanoma to current treatments will ultimately lead to new therapies that will be more effective in cases of advanced cancer.

Published in Cancer Discovery, the study evaluated 573 samples of 387 tumours from 14 patients with advanced melanoma. All the patients had been previously treated with immune checkpoint inhibitor therapies (ICI), but by the time of their deaths, the ICI therapies were no longer effective.

The researchers analyzed the genetic code of individual cells within the tumour samples, looking for patterns that might explain metastasis and treatment resistance. They determined that 11 of the 14 people in the study had lost the genes that enable ICI drugs to help the immune system recognize and attack the cancer. They say this occurs because the cancer can either make multiple copies of defective versions of the genes, or use extrachromosomal DNA to override normal copies of the genes.

"These results present the most detailed picture yet of what melanoma looks like at the final stages of life. We can now see how the cancer evolves to spread to the brain and the liver, and how it can beat the most common treatment currently available for people with advanced disease," said lead investigator of the PEACE study Dr. Mariam Jamal-Hanjani in a press release. She is a Clinical Associate Professor at University College London.

"We now have a huge opportunity to look for new ways to treat advanced cancer. I'm excited about the prospect of more people with cancer having the precious gift of a longer life thanks to research."


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