Growth factor receptors are well-known targets for cancer drugs like Tarceva (erlotinib), Tykerb (lapatinib), and Avastin (bevacizumab), among others.  These receptors activate cell growth by initiating a chain of events that results in progression of the cell cycle which leads to cell division.  You have probably heard about the growth factor receptors EGFR, HER2, and perhaps VEGFR.  One of the limitations of targeting these receptors is that many of them share the same intracellular pathway to activate cell growth.  When just one growth factor receptor is inhibited with a targeted therapy, other receptors can still activate the same downstream growth pathway.

To combat this, scientists are currently developing drugs that target these growth pathways further downstream than the growth factor receptors.  The most common signaling cascade for cancer cell growth involves growth factor receptors activating a protein called Ras, which then activates Raf, which then activates MAPK/ERK kinase (MEK), which then activates ERK.  ERK then directly activates proteins called transcription factors (namely Myc, Elk1, Fos, and Ets) that bind to DNA and tell the cell to make proteins from certain genes that drive cell division forward, such as Cyclin D.  ERK also indirectly activates proteins called RSK that speed up the protein-making machinery inside a cell, allowing the cell division to move ever faster. 

from Pratilas C A , Solit D B Clin Cancer Res 2010;16:3329-3334

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Because this Ras/Raf/MEK/ERK pathway can be activated by multiple growth factor receptors, promising emerging targets in the treatment of cancer are the MEK proteins.    Since many growth signals converge ultimately with the activation of ERK, deactivating MEK should stop ERK from functioning in the cell.  Unfortunately, two of the first MEK inhibitors were discontinued after disappointing phase II clinical trials.  This was most likely due to problems with the specific drug design, however, and newer second-generation MEK inhibitors such as selumetinib demonstrate much better pharmacokinetics.

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