The Therapeutic Potential of MAPK/ERK Inhibitors in the Treatment of Colorectal Cancer
Mehran Pashirzad, Reihaneh Khorasanian, Maryam Mahmoudi Fard, Mohammad‐Hassan Arjmand, Hadis Langari, Majid Khazaei, Saman Soleimanpour, Majid Rezayi, Gordon A. Ferns, Seyed Mahdi Hassanian, Amir Avan
Abstract
The MAPK/ERK signaling pathway regulates cancer cell proliferation, apoptosis, inflammation, angiogenesis, metastasis and drug resistance. Mutations and up-regulation of components of the MAPK/ERK signaling pathway, as well as over-activation of this critical signaling pathway, are frequently observed in colorectal carcinomas. Targeting the MAPK/ERK signaling pathway, using specific pharmacological inhibitors, elicits potent anti-tumor effects, supporting the therapeutic potential of these inhibitors in the treatment of CRC. Several drugs have recently been developed for the inhibition of the MEK/ERK pathway in preclinical and clinical settings, such as MEK162 and MK-2206. MEK1/2 inhibitors demonstrate promising efficacy and anticancer activity for the treatment of this malignancy. This review summarizes the current knowledge on the role of the MAPK/ERK signaling pathway in the pathogenesis of CRC and the potential clinical value of synthetic inhibitors of this pathway in preventing CRC progression for a better understanding, and hence, better management of colorectal cancer.