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Abstract
Cutaneous melanoma causes 55 500 deaths annually. The incidence and mortality rates
of the disease differ widely across the globe depending on access to early detection
and primary care. Once melanoma has spread, this type of cancer rapidly becomes life-threatening.
For more than 40 years, few treatment options were available, and clinical trials
during that time were all unsuccessful. Over the past 10 years, increased biological
understanding and access to innovative therapeutic substances have transformed advanced
melanoma into a new oncological model for treating solid cancers. Treatments that
target B-Raf proto-oncogene serine/threonine-kinase (BRAF)V600 (Val600) mutations
using selected BRAF inhibitors combined with mitogen-activated protein kinase inhibitors
have significantly improved response and overall survival. Furthermore, advanced cutaneous
melanoma has developed into a prototype for testing checkpoint-modulating agents,
which has increased hope for long-term tumour containment and a potential cure. These
expectations have been sustained by clinical success with targeted agents and antibodies
that block programmed cell-death protein 1 in locoregional disease, which induces
prolongation of relapse-free, distant-metastasis-free, and overall survival times.