Liquid Biopsy May Provide Early Warning of Skin Cancer Relapse

Blood test shows new mutations in NRAS and PI3K genes may lead to skin cancer relapse. [iStock/ftwitty]

A blood test may be able to sound early warning bells that patients with advanced melanoma skin cancer are relapsing, according to a study (“Application of Sequencing, Liquid Biopsies and Patient-Derived Xenografts for Personalized Medicine in Melanoma”) published in Cancer Discovery.

Scientists from the Cancer Research UK Manchester Institute studied the DNA shed by tumors into the bloodstream (circulating tumor DNA) in blood samples from seven advanced melanoma patients at The Christie NHS Foundation Trust. In this early work, they found they could see whether a patient was relapsing by tracking levels of circulating tumor DNA. And they found that new mutations in genes like NRAS and PI3K appeared, possibly causing the relapse by allowing the tumor to become resistant to treatment.

Most melanoma patients respond to treatment at first, but their cancer can become resistant within a year. It is hoped that these approaches will allow doctors to use circulating tumor DNA to tailor treatment for individual patients to get the best result.

Around 40–50% of melanoma patients have a faulty BRAF gene, and they can be treated with the targeted drugs vemurafenib or dabrafenib. But for many of these patients the treatments don't work, or their tumors develop resistance after a relatively short time. When this happens, these patients can be offered immunotherapy drugs including pembrolizumab, nivolumab, and ipilimumab. Detecting this situation early could be key to improving their care and chances of survival.

Richard Marais, Ph.D., lead author and Cancer Research UK's skin cancer expert, said “Being able to spot the first signs of relapse, so we can rapidly decide the best treatment strategy, is an important area for research. Using our technique we hope that one day we will be able to spot when a patient's disease is coming back at the earliest point and start treatment against this much sooner, hopefully giving patients more time with their loved ones. Our work has identified a way for us to do this but we still need to test the approach in further clinical trials before it reaches patients in the clinic.”

“One of the sinister things about melanoma is that it can lay dormant for years and then suddenly re-emerge, probably as it escapes from the control of the body's immune system,” added Peter Johnson, M.D., chief clinician of Cancer Research UK.. “Being able to track cancers in real time as they evolve following treatment has huge potential for the way we monitor cancers and intervene to stop them growing back. There's still some time until we see this in the clinic but we hope that in the future, blood tests like these will help us to stay one step ahead in treating cancer.”