Targeting ICMT: A promising strategy in cancer treatment (Review).

Protein prenylation is a prevalent post-translational modification of proteins, pivotal in regulating their biological functions. It influences critical cellular processes such as signal transduction, cell cycle control and apoptosis. Isoprenylcysteine carboxymethyltransferase (ICMT) serves as the terminal enzyme in this pathway, catalyzing the methylation of proteins containing-CAAX or -CXC motifs, thereby modulating their subcellular localization and biological activity. Accumulating evidence indicates that ICMT inhibition disrupts key malignant phenotypes, such as tumor cell proliferation, migration and invasion, and attenuates the functional dependency of RAS proteins on prenylation. Consequently, ICMT has emerged as an important regulator of cancer-associated signaling and a potential therapeutic target. This review summarizes current knowledge on ICMT-mediated protein modification, its regulatory mechanisms and its roles in cancer progression, with the aim of highlighting recent advances and discussing the therapeutic implications of targeting ICMT in oncology.