Colorectal cancer pathogenesis, oncogenic signaling networks and targeted therapeutic advances

Abstract Colorectal cancer (CRC) constitutes a prominent global health burden, being the third most frequently diagnosed malignancy in terms of incidence and the second leading cause of cancer-associated death across the globe. Malignant transformation of colonic epithelial cells stems from the intricate dysregulation of intracellular signal transduction networks. Although targeted therapies have substantially improved patient survival relative to traditional treatments, the complexity of the molecular networks driving carcinogenesis continues to limit the overall prognosis. This review delineates the core signaling cascades governing CRC initiation and progression, with emphasis on the molecular hallmarks of the disease. Drawing on a growing body of high-quality preclinical and clinical evidence, we summarize currently available targeted agents and critically evaluate their underlying mechanisms of action and clinical curative effects, and inherent limitations within the contemporary therapeutic landscape. In addition, we discuss how recent advances in immune checkpoint inhibitors (ICIs) along with a deeper understanding of the tumor microenvironment are shaping global clinical guidelines and revealing promising new targets and combinatorial strategies. In summary, expanding insights into oncogenic signaling pathways are guiding the development of novel treatments and enabling the identification of key elements amenable to pharmacological intervention. Ultimately, this review aims to support the rational design of precise and personalized therapeutic strategies to improve CRC prognosis.