Targeting IκappaB kinases for cancer therapy

Nikee Awasthee, Vipin Rai, Srinivas Chava, Palanisamy Nallasamy, Ajaikumar B. Kunnumakkara, Anupam Bishayee, Subhash C. Chauhan, Kishore B Challagundla, Subash C. Gupta

Research output: Contribution to journalReview article

5 Citations (Scopus)

Abstract

The inhibitory kappa B kinases (IKKs)and IKK related kinases are crucial regulators of the pro-inflammatory transcription factor, nuclear factor kappa B (NF-κB). The dysregulation in the activities of these kinases has been reported in several cancer types. These kinases are known to regulate survival, proliferation, invasion, angiogenesis, and metastasis of cancer cells. Thus, IKK and IKK related kinases have emerged as an attractive target for the development of cancer therapeutics. Several IKK inhibitors have been developed, few of which have advanced to the clinic. These inhibitors target IKK either directly or indirectly by modulating the activities of other signaling molecules. Some inhibitors suppress IKK activity by disrupting the protein-protein interaction in the IKK complex. The inhibition of IKK has also been shown to enhance the efficacy of conventional chemotherapeutic agents. Because IKK and NF-κB are the key components of innate immunity, suppressing IKK is associated with the risk of immune suppression. Furthermore, IKK inhibitors may hit other signaling molecules and thus may produce off-target effects. Recent studies suggest that multiple cytoplasmic and nuclear proteins distinct from NF-κB and inhibitory κB are also substrates of IKK. In this review, we discuss the utility of IKK inhibitors for cancer therapy. The limitations associated with the intervention of IKK are also discussed.

Original languageEnglish (US)
Pages (from-to)12-24
Number of pages13
JournalSeminars in Cancer Biology
Volume56
DOIs
StatePublished - Jun 1 2019

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Phosphotransferases
Neoplasms
Therapeutics
NF-kappa B
Nuclear Proteins
Innate Immunity
Proteins
Transcription Factors

Keywords

  • Cancer therapy
  • IKK inhibitor
  • IKK related kinase
  • Inhibitory kappa B kinase
  • Nuclear factor kappa B

ASJC Scopus subject areas

  • Cancer Research

Cite this

Awasthee, N., Rai, V., Chava, S., Nallasamy, P., Kunnumakkara, A. B., Bishayee, A., ... Gupta, S. C. (2019). Targeting IκappaB kinases for cancer therapy. Seminars in Cancer Biology, 56, 12-24. https://doi.org/10.1016/j.semcancer.2018.02.007

Targeting IκappaB kinases for cancer therapy. / Awasthee, Nikee; Rai, Vipin; Chava, Srinivas; Nallasamy, Palanisamy; Kunnumakkara, Ajaikumar B.; Bishayee, Anupam; Chauhan, Subhash C.; Challagundla, Kishore B; Gupta, Subash C.

In: Seminars in Cancer Biology, Vol. 56, 01.06.2019, p. 12-24.

Research output: Contribution to journalReview article

Awasthee, N, Rai, V, Chava, S, Nallasamy, P, Kunnumakkara, AB, Bishayee, A, Chauhan, SC, Challagundla, KB & Gupta, SC 2019, 'Targeting IκappaB kinases for cancer therapy', Seminars in Cancer Biology, vol. 56, pp. 12-24. https://doi.org/10.1016/j.semcancer.2018.02.007
Awasthee N, Rai V, Chava S, Nallasamy P, Kunnumakkara AB, Bishayee A et al. Targeting IκappaB kinases for cancer therapy. Seminars in Cancer Biology. 2019 Jun 1;56:12-24. https://doi.org/10.1016/j.semcancer.2018.02.007
Awasthee, Nikee ; Rai, Vipin ; Chava, Srinivas ; Nallasamy, Palanisamy ; Kunnumakkara, Ajaikumar B. ; Bishayee, Anupam ; Chauhan, Subhash C. ; Challagundla, Kishore B ; Gupta, Subash C. / Targeting IκappaB kinases for cancer therapy. In: Seminars in Cancer Biology. 2019 ; Vol. 56. pp. 12-24.
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abstract = "The inhibitory kappa B kinases (IKKs)and IKK related kinases are crucial regulators of the pro-inflammatory transcription factor, nuclear factor kappa B (NF-κB). The dysregulation in the activities of these kinases has been reported in several cancer types. These kinases are known to regulate survival, proliferation, invasion, angiogenesis, and metastasis of cancer cells. Thus, IKK and IKK related kinases have emerged as an attractive target for the development of cancer therapeutics. Several IKK inhibitors have been developed, few of which have advanced to the clinic. These inhibitors target IKK either directly or indirectly by modulating the activities of other signaling molecules. Some inhibitors suppress IKK activity by disrupting the protein-protein interaction in the IKK complex. The inhibition of IKK has also been shown to enhance the efficacy of conventional chemotherapeutic agents. Because IKK and NF-κB are the key components of innate immunity, suppressing IKK is associated with the risk of immune suppression. Furthermore, IKK inhibitors may hit other signaling molecules and thus may produce off-target effects. Recent studies suggest that multiple cytoplasmic and nuclear proteins distinct from NF-κB and inhibitory κB are also substrates of IKK. In this review, we discuss the utility of IKK inhibitors for cancer therapy. The limitations associated with the intervention of IKK are also discussed.",
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