RAS-RAF-MEK Pathway: Aberrations and Therapeutic Possibilities

The mitogen-associated protein kinase (MAPK) cascade is a combination of molecular signals that eventually lead to proliferation, survival, differentiation, and cell fate determination. The first identified MAPK network was the RAF-MEK-ERK pathway, which stands for rapidly accelerated fibrosarcoma (RAF), MAPK/ERK kinases (MEK), extracellular signal-regulated kinases (ERK), and, if upregulated, it leads to carcinogenesis. An inherited deregulated MAPK pathway, usually due to heterozygous mutations, causes several phenotypic conditions with cognitive defects, facial dysmorphism, cardiac defects, and increased risk of malignancies. In addition to germline mutations, multiple acquired aberrations have recently been described. These aberrations impact the MAPK pathway in a wide array of malignancies, particularly RAS and BRAF mutations. Targeted therapy using small molecules to inhibit those aberrations has been proven to be beneficial. This chapter describes MAPK pathway mutations and the therapeutic possibilities that might be useful in targeting the associated aberrations.