A comprehensive review on role of Aurora kinase inhibitors (AKIs) in cancer therapeutics

Gupta, Deepali; Kumar, Mukesh; Saifi, Sana; Rawat, Shivani; Ethayathulla, A.S.; Kaur, Punit

doi:10.1016/j.ijbiomac.2024.130913

Cited by 6 publications

(1 citation statement)

References 181 publications

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“…In this summary, we focus on Aurora kinases (AURKs), which are serine/threonine kinases involved in centrosome maturation, spindle assembly, chromosome alignment, and cytokinesis during mitosis (AURK-A, B) and meiosis (AURK-C) [183]. The overexpression of AURKs is observed in various cancers and is linked to metastatic tumor invasiveness and resistance to chemotherapy [184]. AL-8326, a multi-target kinase inhibitor that inhibits Aurora B, FGFRs, and VEGFRs, has shown clinical benefits in Phase Ib/IIa studies for monotherapy in ≥ third-line SCLC patients, with ongoing Phase II and III trials [185].…”

Section: Potential New Targetsmentioning

confidence: 99%

Kinase Inhibitors and Kinase-Targeted Cancer Therapies: Recent Advances and Future Perspectives

Li,

Gong,

Zhou

et al. 2024

IJMS

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Over 120 small-molecule kinase inhibitors (SMKIs) have been approved worldwide for treating various diseases, with nearly 70 FDA approvals specifically for cancer treatment, focusing on targets like the epidermal growth factor receptor (EGFR) family. Kinase-targeted strategies encompass monoclonal antibodies and their derivatives, such as nanobodies and peptides, along with innovative approaches like the use of kinase degraders and protein kinase interaction inhibitors, which have recently demonstrated clinical progress and potential in overcoming resistance. Nevertheless, kinase-targeted strategies encounter significant hurdles, including drug resistance, which greatly impacts the clinical benefits for cancer patients, as well as concerning toxicity when combined with immunotherapy, which restricts the full utilization of current treatment modalities. Despite these challenges, the development of kinase inhibitors remains highly promising. The extensively studied tyrosine kinase family has 70% of its targets in various stages of development, while 30% of the kinase family remains inadequately explored. Computational technologies play a vital role in accelerating the development of novel kinase inhibitors and repurposing existing drugs. Recent FDA-approved SMKIs underscore the importance of blood–brain barrier permeability for long-term patient benefits. This review provides a comprehensive summary of recent FDA-approved SMKIs based on their mechanisms of action and targets. We summarize the latest developments in potential new targets and explore emerging kinase inhibition strategies from a clinical perspective. Lastly, we outline current obstacles and future prospects in kinase inhibition.

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Section: Potential New Targetsmentioning

confidence: 99%

Kinase Inhibitors and Kinase-Targeted Cancer Therapies: Recent Advances and Future Perspectives

Li,

Gong,

Zhou

et al. 2024

IJMS

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Constrained TACC3 peptidomimetics for a non-canonical protein–protein interface elucidate allosteric communication in Aurora-A kinase

Gimenez,

Walko,

Miles

et al. 2025

Chem. Sci.

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MAD2L1 supports MYC-driven liver carcinogenesis in mice and predicts poor prognosis in human hepatocarcinoma

Lu,

Zhang,

Xue

et al. 2024

Toxicological Sciences

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Mitotic arrest deficient 2 like 1 (MAD2L1) is a component of the mitotic spindle assembly checkpoint implicated in cancer cell proliferation and tumorigenesis. The functional role of MAD2L1 in hepatocellular carcinoma (HCC) has not been adequately investigated, especially in vivo. In the current manuscript, we sought to address the function of MAD2L1 in hepatocarcinogenesis. We found that MAD2L1 expression is upregulated in human HCCs, where its expression is associated with higher aggressive tumor grade, elevated proliferative activity, and poor prognosis. In human HCC cell lines, MAD2L1 knockdown led to decreased cell growth. Moreover, RNA-seq results demonstrated that MAD2L1 silencing induces the expression of genes associated with cell cycle, DNA replication, and various cancer-related pathways, supporting the critical role of MAD2L1 during HCC growth and differentiation. In a c-MYC-induced mouse HCC model, we revealed an increased expression of Mad2l1. Furthermore, Mad2l1 CRIPSR-mediated silencing prevented c-MYC-driven mouse liver development. Altogether, our study suggests that MAD2L1 plays a crucial role in hepatocarcinogenesis, and that its suppression could be a promising therapeutic strategy for treating human HCC.

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A comprehensive review on role of Aurora kinase inhibitors (AKIs) in cancer therapeutics

Cited by 6 publications

References 181 publications

Kinase Inhibitors and Kinase-Targeted Cancer Therapies: Recent Advances and Future Perspectives

Kinase Inhibitors and Kinase-Targeted Cancer Therapies: Recent Advances and Future Perspectives

Constrained TACC3 peptidomimetics for a non-canonical protein–protein interface elucidate allosteric communication in Aurora-A kinase

MAD2L1 supports MYC-driven liver carcinogenesis in mice and predicts poor prognosis in human hepatocarcinoma

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