One approach to the study of cancer is genetic profiling, an effort aimed at identifying perturbations in gene expression that lead to the malignant phenotype. However, cancers differ widely in their genetic “signature”, leading to difficulty in diagnosis and treatment, as well as in the development of effective therapeutics.
Genetic profiling of tumors may provide a more effective approach to cancer management and/or treatment. Accordingly, there is a need in the art to better understand the genetic profile of specific classes of tumors, in an effort to provide improved therapeutics, diagnostics and screening methods.
The kinase pathway comprising RAS, RAF, mitogen-activated protein kinase kinase (MEK) and extracellular signal regulated kinase (ERK) is activated in most human tumours, often through gain-of-function mutations of RAS and RAF family members (Davies, H. et al. 2002 Nature 417, 949-954). It has previously been shown that mutation of BRAF is associated with enhanced and selective sensitivity to MEK inhibition. This MEK dependency was observed in BRAF mutant cells regardless of tissue lineage. Since BRAF is a serine/threonine kinase that is commonly activated by somatic point mutation in human cancer, it may provide new therapeutic opportunities in malignant melanoma and other cancers.