Advances in Immunotherapy for Melanoma: A Comprehensive Review

Figure 1

Schematic of the multitude of interacting genetic factors that influence the pathogenesis of melanoma. Oncogenic NRAS mutations activate the effector pathways PI3K-AKT and Raf-MEK-ERK. The latter pathway is also activated by means of mutations in the BRAF gene. In contrast, PI3K-AKT pathway activation is conditioned by the loss or mutation of the tumor suppressor gene PTEN. These changes are generally preserved throughout tumor progression. The development of melanoma has been shown to be strongly associated with the inactivation of the tumor suppressors p16INK4a/cyclin-dependent protein kinases 4 and 6/retinoblastoma (p16INK4a/CDK4,6/pRb) and p14ARF/human double minute 2/p53 (p14ARF/HMD2/P53). Other factors such as microphthalmia-associated transcription factor (MITF) and TP53 play a crucial role in the progression of melanoma [4].