The significant others of aurora kinase a in cancer: combination is the key DOI Creative Commons
Kumar Nikhil, Kavita Shah

Biomarker Research, Journal Year: 2024, Volume and Issue: 12(1)

Published: Sept. 27, 2024

Abstract AURKA is predominantly famous as an essential mitotic kinase. Recent findings have also established its critical role in a plethora of other biological processes including ciliogenesis, mitochondrial dynamics, neuronal outgrowth, DNA replication and cell cycle progression. overexpression numerous cancers strongly associated with poor prognosis survival. Still no AURKA-targeted drug has been approved yet, partially because the collateral toxicity partly due to limited efficacy single agent wide range tumors. Mechanistically, allows it phosphorylate pathological substrates promoting highly aggressive oncogenic phenotypes. Our review examines most recent advances regulation focuses on 33 such direct cancer-specific targets their signaling cascades. One common themes that emerge often involved feedback loop substrates, which could be decisive factor causing sustained upregulation hyperactivation cancer cells, Achilles heel not exploited before. This dynamic interplay between offers potential opportunities for targeted therapeutic interventions. By targeting these may possible disrupt this effectively reverse levels, thereby providing promising avenue developing safer therapeutics. Additionally, exploring synergistic effects inhibition and/or tumor-suppressor provide further effective combination therapies against AURKA-driven cancers, maximizing target.

Language: Английский

Regulation of HDAC6 Catalytic Activity in Cancer: The Role of Post-Translational Modifications and Protein–Protein Interactions DOI Open Access
Leen Asaad,

Benjamin Pepperrell,

Emma McErlean

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(3), P. 1274 - 1274

Published: Feb. 1, 2025

Histone deacetylase 6 (HDAC6) is a large multidomain protein that deacetylates lysine residues on cytoplasmic proteins, influencing numerous cellular processes. Both the catalytic and noncatalytic functions of HDAC6 have been implicated in cancer development progression. Over decade research domain inhibitors has shown these drugs are well tolerated, exhibit anticancer activity, can alleviate chemotherapy-induced peripheral neuropathies. However, their effectiveness treating solid tumours remains uncertain. activity regulated by protein–protein interactions post-translational modifications, which may allosterically influence its domains. As result, effective inhibition using small molecule requires more sophisticated understanding role within tumour cells, including whether expression correlates with activity. A comprehensive cancer-specific expression, functional activation states will be critical for refining use therapy.

Language: Английский

Citations

0
Ultrasmall lactoferrin/lipid multicompartmental nanomedicine-based reprogramming of glycolysis in triple-negative breast cancer via HDAC6/LDH axis enhances cancer immunotherapy DOI
Islam A. Hassanin, Hesham Saeed, Michael G. Shehat

et al.

Chemical Engineering Journal, Journal Year: 2025, Volume and Issue: unknown, P. 163015 - 163015

Published: April 1, 2025

Language: Английский

Citations

0
HDAC6 as a therapeutic target for HPV E7-driven cervical cancer DOI
Wei Jiang, Shanshan Liu, Li Fu

et al.

Genome Instability & Disease, Journal Year: 2025, Volume and Issue: unknown

Published: March 26, 2025

Language: Английский

Citations

0
HDAC6 inhibition by ITF3756 modulates PD-L1 expression and monocyte phenotype: insights for a promising immune checkpoint blockade co-treatment therapy DOI Creative Commons

Valeria Spadotto,

Chiara Ripamonti,

Andrea Ghiroldi

et al.

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: May 13, 2025

Introduction Tumor immunotherapy has revolutionized cancer treatment, particularly through the use of immune checkpoint inhibitors targeting PD-L1/PD-1 axis. While PD-L1 expression on tumor cells is an established predictive biomarker for therapeutic response, emerging evidence highlights importance myeloid cells, both in periphery and within microenvironment (TME). This study explores immunomodulatory effects selective HDAC6 inhibitor ITF3756 monocytes dendritic (DCs). Methods Monocytes were stimulated with pro-inflammatory cytokine TNF-α treated ITF3756. CD40 levels assessed by flow cytometry. Transcriptomic proteomic analyses performed to characterize changes gene protein profiles. T cell proliferation was evaluated co-culture assays. Additionally, impact vivo murine model colon cancer. Results effectively downregulated TNF-α-activated enhanced their costimulatory capacity increasing expression. revealed that counteracted pathway activation multiple inhibitory molecules, promoting a less immunosuppressive phenotype. In assays, ITF3756-treated DCs significantly proliferation. vivo, treatment led reduced growth model. Discussion These findings demonstrate inhibition modulates functionality diminishing signals activation. Thus, represents promising agent could enhance efficacy blockade immunotherapy.

Language: Английский

Citations

0
The significant others of aurora kinase a in cancer: combination is the key DOI Creative Commons
Kumar Nikhil, Kavita Shah

Biomarker Research, Journal Year: 2024, Volume and Issue: 12(1)

Published: Sept. 27, 2024

Abstract AURKA is predominantly famous as an essential mitotic kinase. Recent findings have also established its critical role in a plethora of other biological processes including ciliogenesis, mitochondrial dynamics, neuronal outgrowth, DNA replication and cell cycle progression. overexpression numerous cancers strongly associated with poor prognosis survival. Still no AURKA-targeted drug has been approved yet, partially because the collateral toxicity partly due to limited efficacy single agent wide range tumors. Mechanistically, allows it phosphorylate pathological substrates promoting highly aggressive oncogenic phenotypes. Our review examines most recent advances regulation focuses on 33 such direct cancer-specific targets their signaling cascades. One common themes that emerge often involved feedback loop substrates, which could be decisive factor causing sustained upregulation hyperactivation cancer cells, Achilles heel not exploited before. This dynamic interplay between offers potential opportunities for targeted therapeutic interventions. By targeting these may possible disrupt this effectively reverse levels, thereby providing promising avenue developing safer therapeutics. Additionally, exploring synergistic effects inhibition and/or tumor-suppressor provide further effective combination therapies against AURKA-driven cancers, maximizing target.

Language: Английский

Citations

0