MAP kinase signaling
The mitogen-activated protein (MAP) kinase cell signaling pathway promotes cell growth, proliferation, and survival. The MAP kinase pathway may be activated via several different routes, including upstream growth factor receptor tyrosine kinases and downstream mutations in pathway gene components. 
Figure 1. Binding of a growth factor (e.g., EGF, HGF) to the receptor tyrosine kinase (RTK) activates the receptor's activity. SRC binds to the receptor at its SH2 domain. Activation of the receptor tyrosine kinase triggers downstream phosphorylation and activation of (H-/K-/N-) RAS, (A-/B-/C-) RAF, MEK1/2 (MAP2K1), ERK1/2 (MAPK1). Ultimately, ERK (MAPK1) activation activates gene transcription that regulates cell growth and survival. Specific nodes in the pathway that are therapeutically actionable are noted.
BRAF, KRAS, and NRAS are the most frequent biomarkers that serve as inclusion criteria in therapies targeting the MAP kinase signaling pathway.
Biomarkers in the MAP kinase signaling pathway serve as inclusion eligibility criteria in 284 clinical trials, of which 209 are open and 75 are closed. The genes BRAF, KRAS, NRAS, HRAS, and CRKL on this pathway most frequently harbor alterations that are inclusion eligibility criteria for clinical trials.
Of the trials that contain alteration(s) in the MAP kinase signaling pathway as inclusion criteria, 2 are early phase 1 (2 open), 1 is n/a (1 open), 92 are phase 1 (57 open), 56 are phase 1/phase 2 (45 open), 116 are phase 2 (90 open), 2 are phase 2/phase 3 (1 open), 14 are phase 3 (12 open), and 1 is phase 4 (1 open) .