NF-κB and apoptosis: colorectal cancer progression and novel strategies for treatment

Colorectal cancer (CRC), the third most prevalent cancer worldwide, presents a significant burden in terms of both mortality and morbidity. The development of CRC is a complex process, driven by a combination of genetic mutations and epigenetic alterations that disrupt normal cellular functions. These changes influence a range of cancer-regulating mechanisms, including metabolism, cell proliferation, invasion, metastasis, and apoptosis. Apoptosis, a crucial process in maintaining cellular homeostasis, plays a paradoxical role in CRC progression. While it helps eliminate damaged cells, the evasion of apoptosis allows cancer cells to thrive, gain nutrients, and avoid metabolic waste accumulation, thereby facilitating tumor growth. Additionally, the process of neovascularization, the formation of new blood vessels, is critical for tumor sustenance and expansion. The nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathway is a key regulator involved in multiple physiological and pathological processes, including angiogenesis, tumor migration, cell proliferation, inflammation, apoptosis, and differentiation. Dysregulation of NF-κB activity is implicated in the progression of CRC. This review provides a comprehensive evaluation of the role of NF-κB signaling in CRC, particularly its involvement in apoptosis. Moreover, it explores the therapeutic potential of targeting the NF-κB pathway with natural and synthetic compounds, highlighting their ability to modulate CRC progression and improve patient outcomes. These insights underscore the potential of NF-κB inhibition as a novel therapeutic strategy in CRC management.