Colorectal Cancer: Etiology, Pathogenesis, and Therapeutic Advances

Colorectal cancer (CRC), a malignancy arising in the colon or rectum due to the uncontrolled division of aberrant cells, represents a significant global health challenge. It ranks as the third most diagnosed cancer and the second leading cause of cancer-related death worldwide. CRC's development is complex, involving a multi-factorial interaction of genetic components, lifestyle, and inflammation, and most often presents as the sporadic type (approximately 75% of cases). This review summarizes the current understanding of CRC, spanning its etiology and modifiable risk factors, the multi-step pathogenesis from aberrant crypt foci (ACF) to metastasis, the crucial role of molecular genetics [chromosomal instability (CIN) and microsatellite instability (MSI) pathways], modern classification systems and prognostic indicators, and the evolution of treatment strategies toward precision medicine. Special focus is given to the deregulated inflammatory and molecular signaling pathways [such as phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR), mitogen-activated protein kinase (MAPK), and transforming growth factor-beta (TGF-β)) that drive carcinogenesis, invasion (epithelial-mesenchymal transition (EMT)], and therapeutic resistance.