Targeting molecular and genetic pathways driving tumorigenesis for precision therapy in colorectal cancer

Colorectal cancer (CRC) remains a major global health challenge and a leading cause of cancer-related mortality worldwide. Central to its pathogenesis is the dysregulation of interconnected signal transduction networks that govern cellular proliferation, survival, differentiation, apoptosis, and immune modulation. Progressive disruption of these pathways facilitates malignant transformation of the colonic epithelium and underlies disease initiation and progression. In this review, we examine the foundational signaling mechanisms implicated in CRC, with an emphasis on the Wnt/β-catenin, GUCY2C, MAPK/ERK, p53, PI3K/AKT, and SMAD4/TGF-β pathways. We also highlight the genomic and epigenomic hallmarks of CRC to illustrate how genetic and epigenetic alterations contribute to diverse oncogenic processes. Furthermore, we discuss both conventional and emerging precision-based therapeutic strategies aimed at driving mutations in CRC tumorigenesis. By synthesizing advances in signaling biology, this review aims to provide a framework for understanding CRC complexity and to inform the development of more precise and effective therapies.