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Targeting IκappaB kinases for cancer therapy
Nikee Awasthee1, Vipin Rai1, Srinivas Chava2
1Laboratory for Translational Cancer Research, Department of Biochemistry, Institute of Science, Banaras Hindu University, Varanasi 221005, Uttar Pradesh, India.
Seminars in Cancer Biology
|February 28, 2018
Summary
Inhibitory kappa B kinases (IKKs) regulate nuclear factor kappa B (NF-κB) in cancer. IKK inhibitors show therapeutic potential but carry risks like immune suppression and off-target effects.
Area of Science:
- Molecular Biology
- Cancer Biology
- Immunology
Background:
- Inhibitory kappa B kinases (IKKs) and related kinases are key regulators of nuclear factor kappa B (NF-κB).
- Dysregulated IKK activity is implicated in various cancers, influencing cell survival, proliferation, invasion, angiogenesis, and metastasis.
- IKK and NF-κB are central to innate immunity.
Purpose of the Study:
- To review the therapeutic utility of IKK inhibitors in cancer treatment.
- To discuss the limitations and potential side effects associated with IKK inhibition.
Main Methods:
- Literature review of studies on IKK inhibitors and their mechanisms.
- Analysis of clinical advancements and challenges of IKK-targeted therapies.
- Exploration of off-target effects and alternative substrates of IKK.
Main Results:
- Several IKK inhibitors have been developed, with some progressing to clinical trials.
- IKK inhibitors can target IKK directly or indirectly, including disrupting protein-protein interactions.
- Inhibition of IKK can enhance chemotherapy efficacy but poses risks of immune suppression and off-target effects due to IKK's role in innate immunity and its diverse substrates.
Conclusions:
- IKK and IKK-related kinases are promising therapeutic targets for cancer.
- While IKK inhibitors offer potential benefits, careful consideration of immune suppression and off-target effects is crucial.
- Further research is needed to optimize IKK-targeted therapies and mitigate associated risks.
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