File:Melanoma drugs and their target pathways.jpeg

Drugs developed to treat melanoma (top) and their targets (below) in several of the main pathways involved in melanoma initiation, progression and maintenance are indicated by different colours. One such pathway is the three-tiered Ras/Raf/MEK mitogen-activated protein kinase (MAPK) signalling module. Another is the PI(3)K pathway, which regulates cell survival, proliferation, growth and motility, and is inhibited by the lipid phosphatase PTEN. The involvement of signalling by NF-kappaB, which transcribes various genes including matrix metalloproteases (which are involved in metastasis), IAPs and Bcl-2 (anti-apoptotic factors), and VEGF and cytokines (which partake in angiogenesis), is also shown. However, upstream NF-kappaB signals are omitted for simplicity. The schematic includes interactions between MAPK, PI(3)K and NF-kappaB signalling. The p16INK4a/RB and ARF signalling pathways are also important, as their disruption can lead to melanoma by preventing melanocyte senescence.

Reprinted by permission from Macmillan Publishers Ltd: Nature Publishing Group. Gray-Schopfer, et. al. Melanoma biology and new targeted therapy. Nature 445, 851-857(22 February 2007)