Melanoma: predicting immunotherapy-induced side effects

Source: Drug Target Review, August 2024

Scientists at NYU Langone Health and its Perlmutter Cancer Center have revealed that an activity pattern in genes that build spleen tyrosine kinases can predict which melanoma patients are likely to have severe side effects from immunotherapy.

Melanoma is the deadliest form of skin cancer, causing almost 10,000 American deaths per year. Although checkpoint inhibitors like nivolumab and ipilimumab are frequently used to treat this disease, over one third of melanoma patients treated with these develop severe side effects, including inflammation, skin rashes, liver toxicity, colitis and rheumatoid arthritis. This affects their quality of life and their ability to continue treatment.

In the new study the team discovered, even before treatment began, that 83 percent of melanoma patients who eventually developed severe side effects from combined immunotherapy with nivolumab and ipilimumab, was predicted by the activity of genes controlling the production of spleen tyrosine kinases. Furthermore, they observed that this increased gene signature, shown by the production of spleen tyrosine kinases or the SYK pathway, did not interfere with the effectiveness of therapies stopping melanoma recurrence. The impact was solely linked to side effects.

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