Targeting the NF-κB Pathway in Cancer Therapy

Most NF-κB inhibitors target the IKK complex, IκB proteins, or NF-κB transcription factors. The most promising classes of inhibitors include antioxidants, antiinflammatory compounds, natural compounds, statins, proteasome inhibitors, IKKβ inhibitors, biologics, gene therapy, and RNA interference. Targeting NF-κB is limited by intrinsic pathway complexity, cross-talk with other pathways, a lack of biomarkers, poor drug specificity, drug resistance, and difficulty with drug delivery. Future NF-κB targeting will be improved through better understanding of the pathway, more specific inhibitors, and multimodality therapies.

Key points

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NF-κB comprises a family of transcription factors that stimulate tumor promotion and progression, chemoresistance, and radioresistance.
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Hundreds of NF-κB inhibitors have been documented that target 3 main pathway sites of signaling integration: the IKK complex, IκBs and NF-κB transcription factors.
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Most NF-κB inhibitors such as synthetic IKKβ inhibitors, interfering RNAs, and gene therapy are not yet in clinical trial.
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Targeting NF-κB is limited by intrinsic pathway complexity, cross-talk with other pathways, lack of biomarkers, poor drug specificity, drug resistance, and drug delivery limitations.
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Future NF-κB targeting will be improved by better understanding of the pathway, more specific inhibitors, and multimodality therapies, which will reduce resistance and increase efficacy.