The mitogen-activated protein kinase cascade (MAPK/ERK pathway) is a signaling pathway activated as a cellular response to various stimuli and for regulating the proliferation and survival of several types of eukaryotic cells, among others a wide variety of tumor cells. Mutations of the proteins involved in this pathway have been discovered in several tumor entities, indicating their inhibition as a potential therapeutic target. BRAF inhibitors have been in the clinical use since 2011. Several MEK inhibitors have been studied for metastatic cancer treatment in the recent past. After trametinib, cobimetinib is another potent, selective oral MEK1/2 inhibitor that was approved by European Medicine Agency (EMA) and Food and Drug Administration (FDA) in 2015 for treatment of malignant melanoma in a combination with the BRAF inhibitor vemurafenib.
Keywords: BRAF/MEK inhibition; Cobimetinib; Combination therapy; MAPK/ERK pathway; MEK inhibitors.