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. Author manuscript; available in PMC: 2016 Jan 31.
Published in final edited form as: J Invest Dermatol. 2015 Aug;135(8):1929–1933. doi: 10.1038/jid.2015.14

Figure 1.

Figure 1

Molecular targeting of the mitogen-activated protein kinase (MAPK), PI3K, and CDK4 pathways and the associated mutation rates of potential molecular targets in advanced melanoma (Hodis et al., 2012). Activation of a receptor tyrosine kinase such as c-KIT results in the propagation of signal via the MAPK pathway leading to activation of RAS, RAF, MEK and ERK. This ultimately results in the gene expression and promotes cellular proliferation and survival. Mutated BRAF bypasses this ordered pathway and stimulates constitutive signaling, making it a prime target for vemurafenib and dabrafenib. Trametinib targets the downstream effector molecule MEK. Dysregulation of the PI3K pathway promotes melanoma progression. Small molecule inhibitors of the PI3K pathway are being clinically tested in combination with MAPK pathway inhibition. Similarly, CDK4 is an attractive candidate molecule to target in melanoma and is the focus of multiple clinical trials. Red=activated; gray=inactivated; green=normal function. Drugs (shown in boxes) that have been approved (bold), or in trial (non-bold, italics), are indicated.