Scientists have discovered how some skin cancers stop responding to treatment at the end of life. An in-depth analysis of 14 patients who died from incurable melanoma has revealed that changes to the order, structure and number of copies of tumour DNA could cause some skin cancers to resist treatment. These changes also explain how melanoma can spread to other parts of the body.
The research, published today (29th March) in Cancer Discovery, was led by scientists and clinicians at the Francis Crick Institute, UCL and The Royal Marsden. It is part of the Cancer Research UK-funded PEACE study, which is shedding light on the final stages of life with cancer by analysing tumour samples taken from autopsies with informed consent. Additional funding for this research was provided by Melanoma Research Alliance, The Royal Marsden Cancer Charity and Rosetrees.
The scientists found that 11 out of the 14 patients in the study had lost functioning genes that play a role in enabling checkpoint inhibitors (drugs that help the immune system recognise and attack the cancer). This loss occurs because the cancer can either make multiple copies of defective versions of the genes, or use circular rings of DNA from outside the chromosome (called extrachromosomal DNA) to override normal copies of the genes.
Consultant Medical Oncologist at the Melanoma Unit at the Royal Marsden and Research Group Leader at the Francis Crick Institute, Professor Samra Turaljic, said: “We found that melanoma can profoundly alter its genome to hide from the immune system and spread around the body. These profound changes are highly complex, but we’re hopeful that we can now find ways to target them in the clinic.”