Targeting the NF-κB Pathway in Cancer: Mechanisms, Resistance, and Therapeutic Potential Across Tumor Types

Cancer remains a leading cause of death, and current therapeutic options designed to slow the progression of cancer or eradicate cancer cells are often limited by drug resistance, inefficacy, or adverse effects. The Nuclear Factor Kappa B (NF-κB) pathway is a central regulator of inflammation and immune responses, and its dysregulation contributes to cancer development and progression. This review provides an overview of the role of the NF-κB pathway in tumor development and progression and discusses the potential of targeting specific modulators of the pathway for cancer drug discovery, specifically cancers that have the highest prevalence, such as breast, colorectal, lung, melanoma, and prostate cancers. While NF-κB inhibitors show promise, particularly in hematologic malignancies, challenges remain in translating these findings to solid tumors due to pathway complexity and its essential role in normal immunity.