Simplified schematics of the MAPK and PI3K pathways in melanoma and the clinical compounds available for their inhibition

Simplified schematics of the MAPK and PI3K pathways in melanoma and the clinical compounds available for their inhibition. In the absence of BRAF mutations, receptor tyrosine kinases are activated by their ligands and activate RAS and PI3K. RAS then activates the RAF/MEK/ERK signaling cascade which eventually provides survival, proliferation, invasion, and angiogenesis advantages to melanoma tumors. BRAF mutant melanoma cells are sensitive to BRAF inhibitors but resistance can occur via a RAF isoform switch and other compensatory pathways. Combinatorial approaches targeting more than one molecule within one pathway or several pathways simultaneously need to be carefully investigated as potential treatment options for melanomas refractory to BRAF inhibitors. Compounds targeting the MAPK and PI3K pathways, and currently being tested in clinic trials, are indicated.

Publication

Targeting BRAF in advanced melanoma: a first step towards manageable disease. () Adina Vultur, et al. Clin Cancer Res. ;17(7):1658-1663. Figure: F1. All organisms Mus musculus Homo sapiens Drosophila melanogaster

Disease mentions