ERK1/2 inhibitors MK-8353,9 GDC0994,12 CC-9000313 and BVD-52314 have been proved to accompany with adverse effects in clinical trials, such as interacting with other drugs or affecting the physiological function of normal cells, limiting their long-term use in the clinic.15 In addition, cancer cells are highly adaptable and can easily develop acquired resistance in the course of long-term use of ERK1/2 inhibitors. The gene discussed is MAPK3; the disease is cancer.