Colomer Carlota, Pecharroman Irene, Bigas Anna, Espinosa Lluís
Cancer Research Program, Institut Mar d'Investigacions Mèdiques, CIBERONC, Hospital del Mar, Barcelona 08003, Spain.
Cancer Drug Resist. 2020 Mar 21;3(3):482-490. doi: 10.20517/cdr.2019.104. eCollection 2020.
Cancer therapy has improved considerably in the last years; however, therapeutic resistance is still a major problem that impedes full response to the treatment and the main cause of patient relapse and death. Numerous kinases have been reported to be overactivated in cancer and induce resistance to current therapies. Targeting kinases has proven to be useful for overcoming chemotherapy resistance and thus improving patient outcomes. Inhibitor of kappaB kinase alpha (IKKα) is a serine/threonine kinase that was first described as part of the IKK complex in the nuclear factor-κB (NF-κB) pathway, which regulates several physiological and physiopathological processes such as immunity, inflammation, and cancer. However, the IKKα subunit has been shown to be dispensable for NF-κB activation and responsible of multiple pro-tumorigenic functions. Furthermore, we identified a nuclear active form of IKKα kinase IKKα(p45) that promotes tumor growth and therapy resistance, independent of canonical NF-κB. Improved understanding of resistance mechanisms will facilitate drug discovery and provide new effective therapies. Here, we review the recent publications on the implications of IKKα in cancer initiation, development, and resistance.
在过去几年中，癌症治疗有了显著改善；然而，治疗耐药性仍然是一个主要问题，它阻碍了对治疗的完全反应，也是患者复发和死亡的主要原因。据报道，许多激酶在癌症中过度激活，并导致对当前疗法产生耐药性。事实证明，靶向激酶有助于克服化疗耐药性，从而改善患者预后。κB激酶α（IKKα）抑制剂是一种丝氨酸/苏氨酸激酶，最初被描述为核因子κB（NF-κB）通路中IKK复合物的一部分，该通路调节多种生理和病理生理过程，如免疫、炎症和癌症。然而，已证明IKKα亚基对于NF-κB激活并非必需，而是具有多种促肿瘤发生功能。此外，我们鉴定出一种核活性形式的IKKα激酶IKKα(p45)，它促进肿瘤生长和治疗耐药性，独立于经典NF-κB。对耐药机制的深入了解将有助于药物研发，并提供新的有效治疗方法。在此，我们综述了最近关于IKKα在癌症起始、发展和耐药性方面影响的出版物。
