Genetic mistakes may affect skin cancer patient response to treatment
The B-Raf protein inhibited during treatment. Credit: Wikipedia
Researchers from our Departments of Cancer Studies and Molecular Medicine and Biochemistry, funded by Cancer Research UK, studied a group of rare inherited developmental disorders called RASopathies, which are also caused by faults in the gene BRAF, but not the common fault that causes melanoma.
They studied a specific rare fault in BRAF called L597V, which was not found to cause cancer on its own. But when a second gene, RAS, was faulty too and tumours developed although the biology driving the cancers was subtly different. Crucially this meant that the drug vemurafenib, used in the treatment of melanoma, had an opposite effect meaning it actually boosted cancer growth.
The findings, published in the journal Genes and Development on Monday, show that certain rare gene faults in the tumours of patients receiving vemurafenib may also explain why some patients develop secondary non-melanoma skin cancers.
Vemurafenib works by targeting a common fault in the gene BRAF, called V600E, which is present in at least half of melanoma skin cancers. The drug stops BRAF from activating a key pathway that drives cancer growth. But this common fault is not present in all people who develop melanoma and around 18 per cent of patients given the drug go on to develop other, less serious, forms of non-melanoma skin cancer.
