Promising Therapy in Lung Cancer: Spotlight on Aurora Kinases

Galetta, Domenico; Cortes-Dericks, Lourdes

doi:10.3390/cancers12113371

Cited by 31 publications

(22 citation statements)

References 76 publications

(57 reference statements)

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“…Accordingly, the AURKs, in particular AURKA and B were proposed as promising targets for cancer therapy, e.g. in lung cancer treatment ( Galetta and Cortes-Dericks, 2020 ), where AURK inhibition is currently evaluated in clinical trials. In view of recent findings, indicating therapeutic benefit of combined inhibition of IGF2BP1-RNA binding by BTYNB and the CDK4/6 inhibitor palbociclib, the identification of conserved upregulation of AURKA by IGF2BP1 suggests that IGF2BP1 inhibition may improve AURKA-inhibition in combined therapies ( Müller et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

IGF2BP1, a Conserved Regulator of RNA Turnover in Cancer

Glaß

Misiak

Bley

et al. 2021

Front. Mol. Biosci.

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The oncofetal IGF2 mRNA-binding protein 1 (IGF2BP1) promotes tumor progression in a variety of solid tumors and its expression is associated with adverse prognosis. The main role proposed for IGF2BP1 in cancer cells is the stabilization of mRNAs encoding pro-oncogenic factors. Several IGF2BP1-RNA association studies, however, revealed a plethora of putative IGF2BP1-RNA targets. Thus, at present the main conserved target RNAs and pathways controlled by IGF2BP1 in cancer remain elusive. In this study, we present a set of genes and cancer hallmark pathways showing a conserved pattern of deregulation in dependence of IGF2BP1 expression in cancer cell lines. By the integrative analysis of these findings with publicly available cancer transcriptome and IGF2BP1-RNA association data, we compiled a set of prime candidate target mRNAs. These analyses confirm a pivotal role of IGF2BP1 in controlling cancer cell cycle progression and reveal novel cancer hallmark pathways influenced by IGF2BP1. For three novel target mRNAs identified by these studies, namely AURKA, HDLBP and YWHAZ, we confirm IGF2BP1 mRNA stabilization. In sum our findings confirm and expand previous findings on the pivotal role of IGF2BP1 in promoting oncogenic gene expression by stabilizing target mRNAs in a mainly 3’UTR, m6A-, miRNA-, and potentially AU-rich element dependent manner.

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Section: Discussionmentioning

confidence: 99%

IGF2BP1, a Conserved Regulator of RNA Turnover in Cancer

Glaß

Misiak

Bley

et al. 2021

Front. Mol. Biosci.

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“…A variety of small molecule inhibitors to target AURKs have been developed and are in different phases of clinical trials. The development of AURKA inhibitors and their progress has been described recently [ 7 ]. The possibility of targeting AURKB has gained momentum during last few years.…”

Section: Targeting Aurkb In Cancermentioning

confidence: 99%

“…Overexpression of AURKs in tumors has been shown to trigger aneuploidy and genomic instability [ 6 ] that leads to tumor development, invasion and metastasis. AURKA and its functions have been widely investigated and several reviews were authored to highlight its importance in cancer [ 7 , 8 ]. The role of AURKC in cancer is not completely understood and needs further investigations.…”

Section: Introductionmentioning

confidence: 99%

Aurora Kinase B Inhibition: A Potential Therapeutic Strategy for Cancer

2021

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Aurora kinase B (AURKB) is a mitotic serine/threonine protein kinase that belongs to the aurora kinase family along with aurora kinase A (AURKA) and aurora kinase C (AURKC). AURKB is a member of the chromosomal passenger protein complex and plays a role in cell cycle progression. Deregulation of AURKB is observed in several tumors and its overexpression is frequently linked to tumor cell invasion, metastasis and drug resistance. AURKB has emerged as an attractive drug target leading to the development of small molecule inhibitors. This review summarizes recent findings pertaining to the role of AURKB in tumor development, therapy related drug resistance, and its inhibition as a potential therapeutic strategy for cancer. We discuss AURKB inhibitors that are in preclinical and clinical development and combination studies of AURKB inhibition with other therapeutic strategies.

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“…Although Mibefradil was proved to have therapy effect in several tumor types, such as leukemia [41] and glioblastoma [42], its anti-tumor pharmacologic mechanism was never elucidated clearly. In this study, through target prediction and molecular docking, we found AURKA, a serine or threonine kinase [43,44], was the therapy target for Mibefradil in TNBC. Mibefradil treatment could inhibit the expression and phosphorylation of AURKA, which finally led to apoptosis enhancement in TNBC.…”

Section: Discussionmentioning

confidence: 87%

Mibefradil inhibits the proliferation of triple-negative breast cancer by targeting AURKA to regulate apoptosis signal pathway

Han

Liu³

et al. 2021

Preprint

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Background: Triple negative breast cancer (TNBC) is a tumor characterized by high recurrence and mortality, but without effective targeted therapy. It is urgent to explore new treatment strategy to improve the efficacy of TNBC therapy. Methods: Transcriptomic profiling datasets of TNBC were used for screening TNBC specific gene sets. Drug prediction was performed in Connectivity map (CMap) database. Molecular docking method was used for analyzing drug targets. In vitro and in vivo models of TNBC were constructed to examine the drug efficacy. Results: We screened out Mibefradil, a T-type Ca2+ channel blocker, might be a potential therapeutic drug for TNBC by transcriptomics and bioinformatics analysis, and verified that Mibefradil could inhibit the proliferation of TNBC cells by inducing apoptosis and cell cycle arrest. Furthermore, by network pharmacology and molecular docking analysis, AURKA was predicted as the most possible drug target of Mibefradil. Finally, it was proved that Mibefradil treatment could induce apoptosis by decreasing protein expression and phosphorylation level of AURKA in vitro and in vivo. Conclusions: Mibefradil played anti-cancer role in TNBC cells by targeting to AURKA to induce cell cycle and apoptosis. Our results repurposed Mibefradil as a potential targeted drug of TNBC and provided a fundamental research for a novel strategy TNBC treatment.

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Promising Therapy in Lung Cancer: Spotlight on Aurora Kinases

Cited by 31 publications

References 76 publications

IGF2BP1, a Conserved Regulator of RNA Turnover in Cancer

IGF2BP1, a Conserved Regulator of RNA Turnover in Cancer

Aurora Kinase B Inhibition: A Potential Therapeutic Strategy for Cancer

Mibefradil inhibits the proliferation of triple-negative breast cancer by targeting AURKA to regulate apoptosis signal pathway

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