Abstract:: Colorectal Cancer (CRC) is the third most prevalent malignancy, with a high mortality rate. Ageing is a key risk factor connected with this colon- or rectumaffecting malignancy. Aberrant activation of oncogenic signaling pathways, such as MAPK/ERK, PI3K/AKT, and Notch, is frequently exhibited in CRC. The MAPK/ERK signaling cascade, as part of a broader cellular signaling network, plays a prominent role in orchestrating many biological processes. Stimulation of receptors implicated in this pathway by a wide spectrum of ligands leads to an upregulation in the expression of target genes by phosphorylated ERK. Cutting-edge molecular profiling has elucidated various mutational alterations within the MAPK/ERK pathway, with a noticeable focus on KRAS and BRAF mutant variants. Various facets of CRC advancement are intricately related to ERK hyperactivity. Prominent developmental phenomena attributed to this signaling cascade encompass elevated cellular proliferation, maintenance of the cancer stem-cell population, drug resistance, facilitation of angiogenesis, and increased invasive and migratory potential in CRC. Due to the profound role of ERK in the evolutionary stages of CRC, solving this problem depends on deepening our understanding of the ERK signaling pathway. In the domain of advancing CRC therapies, the design of personalized treatment plans assumes specific significance. The detection of KRAS and BRAF mutations in patients can be a predictive marker of therapy response and clinical outcome. By integrating recent insights, this article aims to review the complexities of MAPK/ERK's role in CRC progression and its notable potential in the development of more effective, targeted therapeutic approaches.
Molavand et al. (2026) studied this question.