The members of the RAS–RAF–MEK–ERK signaling pathway and cancer

Abstract

Cancer is one of the biggest health problems of contemporary humanity, representing the second cause of death after cardiovascular diseases, caused by many contributing factors, such as population growth, ageing, stress, pollution, unhealthy diet, tumor diversity and heterogenity, difficulties in correct and early diagnosis and inefficiency of current treatments (e.g. cytoreduction, chemotherapy, radiotherapy, etc.). This leads us to look for new ways of dealing with cancer, such as immunotherapy and personalized therapy, which consider the type of tumour, mutations and expression levels of certain genes, making it necessary to detect specific markers. A category of such specific markers is represented by the proteins involved in inter- and intra-cellular signaling which play essential roles in tumor transformation, progression and dissemination. In cancer, some canonical signaling pathways, including RAS-RAF-MEK-ERK, P13K-PKB/AKT, JAK-STAT, HIF1-VEGF, TGFB, NOTCH, RAP1, TP53, B-catenin/WNT, HIPPO, KEAP-NRF2, MYC and CDKN2 (cell cycle), may be dysregulated. In this review, we detail the roles of RAS–RAF–MEK–ERK signaling pathway in tumorigenic processes and the types of abnormalities that affect them in cancer.