Molecular Pathways: The Balance between Cancer and the Immune System Challenges the Therapeutic Specificity of Targeting Nuclear Factor-κB Signaling for Cancer Treatment.

The Nuclear Factor-κB (NF-κB) signaling pathway is a complex network linking extracellular stimuli to cell survival and proliferation. Cytoplasmic signaling to activate NF-kB can occur as part of the DNA damage response or in response to a large variety of activators including viruses, inflammation, and cell death. NF-κB transcription factors play a fundamental role in tumorigenesis and are implicated in the origination and propagation of both hematologic and solid tumor types, including melanoma, breast, prostate, ovarian, pancreatic, colon, lung, and thyroid cancers. On the other hand, NF-kB signaling is key to immune function, and is likely necessary for anti-tumor immunity. This presents a dilemma when designing therapeutic approaches to target NF-kB. There is growing interest in identifying novel modulators to inhibit NF-κB activity since impeding different steps of the NF-κB pathway has potential to slow tumor growth, progression, and resistance to chemotherapy. Despite significant advances in our understanding of this pathway, our ability to effectively clinically block key targets for cancer therapy remains limited due to on-target effects in normal tissues. Tumor specificity is critical to developing therapeutic strategies targeting this anti-apoptotic signaling pathway in order to maintain anti-tumor immune surveillance when applying such therapy to patients.

Clinical cancer research : an official journal of the American Association for Cancer Research. 2016 Jul 15 [Epub ahead of print]

Kristen P Zeligs, Monica K Neuman, Christina M Annunziata

Women's Malignancies Branch, National Cancer Institute., Women's Malignancies Branch, National Cancer Institute., Women's Malignancies Branch, NCI/NIH .