Combining histone deacetylase inhibitors (HDACis) with other therapies for cancer therapy

Zhou, Mengjiao; Yuan, Minjian; Zhang, Meng; Lei, Chenyi; Aras, Ömer; Zhang, Xiaohong; An, Feifei

doi:10.1016/j.ejmech.2021.113825

Cited by 48 publications

(19 citation statements)

References 168 publications

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“…Moreover, we found 6 JMJD8-related compounds showing HDAC inhibitors’ MoA. Since histone deacetylation is a switch of DNA repair ( 55 ), we also doubted whether JMJD8 controls the chromatin deacetylation to trigger DNA repair. To answer these questions, future efforts should be focused on finding the direct effects that JMJD8 mediates, and this study pointed the way.…”

Section: Discussionmentioning

confidence: 86%

JMJD8 Is an M2 Macrophage Biomarker, and It Associates With DNA Damage Repair to Facilitate Stemness Maintenance, Chemoresistance, and Immunosuppression in Pan-Cancer

et al. 2022

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BackgroundJMJD8 has recently been identified as a cancer-related gene, but current studies provide limited information. We aimed to clarify its roles and the potential mechanisms in pan-cancer.MethodsPan-cancer bulk sequencing data and online web tools were applied to analyze JMJD8’s correlations with prognosis, genome instability, cancer stemness, DNA repair, and immune infiltration. Moreover, single-cell datasets, SpatialDB database, and multiple fluorescence staining were used to validate the association between JMJD8 expression and M2 macrophages. Further, we utilized ROCplotter and cMap web tool to analyze the therapeutic responses and screened JMJD8-targeted compounds, respectively, and we used AlphaFold2 and Discovery Studio to conduct JMJD8 homology modeling and molecular docking.ResultsWe first noticed that JMJD8 was an oncogene in many cancer types. High JMJD8 was associated with lower genome stability. We then found that high JMJD8 correlated with high expression of mismatch repair genes, stemness, homologous repair gene signature in more than 9 cancers. ESTIMATE and cytokine analyses results presented JMJD8’s association with immunosuppression. Also, immune checkpoint CD276 was positively relevant to JMJD8. Subsequently, we validated JMJD8 as the M2 macrophage marker and showed its connection with other immunosuppressive cells and CD8+ T-cell depression. Finally, potential JMJD8-targeted drugs were screened out and docked to JMJD8 protein.ConclusionWe found that JMJD8 was a novel oncogene, and it correlated with immunosuppression and DNA repair. JMJD8 was highly associated with immune checkpoint CD276 and was an M2 macrophage biomarker in many cancers. This study will reveal JMJD8’s roles in pan-cancer and its potential as a novel therapeutic target.

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Section: Discussionmentioning

confidence: 86%

JMJD8 Is an M2 Macrophage Biomarker, and It Associates With DNA Damage Repair to Facilitate Stemness Maintenance, Chemoresistance, and Immunosuppression in Pan-Cancer

et al. 2022

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“…HDACi are classified into four classes based on their chemical. In addition to in vitro and in vivo studies, hydroxamates and aliphatic acids have also been tested in clinical trials as a new treatment strategy for hepatobiliary cancer [ 61 , 62 , 63 , 64 ]. Panobinostat, trichostatin A, vorinostat, and belinostat are hydroxamates that block HDAC activity by binding to Zn 2+ at the HDAC binding site.…”

Section: Inhibitors Of Histone Modificationmentioning

confidence: 99%

Polyphenols as Potent Epigenetics Agents for Cancer

Rajendran

Abdelsalam

Renu

et al. 2022

IJMS

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Human diseases such as cancer can be caused by aberrant epigenetic regulation. Polyphenols play a major role in mammalian epigenome regulation through mechanisms and proteins that remodel chromatin. In fruits, seeds, and vegetables, as well as food supplements, polyphenols are found. Compounds such as these ones are powerful anticancer agents and antioxidants. Gallic acid, kaempferol, curcumin, quercetin, and resveratrol, among others, have potent anti-tumor effects by helping reverse epigenetic changes associated with oncogene activation and tumor suppressor gene inactivation. The role dietary polyphenols plays in restoring epigenetic alterations in cancer cells with a particular focus on DNA methylation and histone modifications was summarized. We also discussed how these natural compounds modulate gene expression at the epigenetic level and described their molecular targets in cancer. It highlights the potential of polyphenols as an alternative therapeutic approach in cancer since they modulate epigenetic activity.

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“…(a) Drug resistance: Although combination therapy can often reduce drug resistance, in some cases patients can become resistant to combination therapies [ 147 , 148 ]. This can involve multiple factors, including a complex tumor microenvironment, drug efflux, cancer stem cells, bulk tumor cells, and crosstalk between signaling pathways.…”

Section: Advantages and Challenges In The Use Of Combination Therapy ...mentioning

confidence: 99%

Current Molecular Combination Therapies Used for the Treatment of Breast Cancer

Wang

Minden

2022

IJMS

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Breast cancer is the second leading cause of death for women worldwide. While monotherapy (single agent) treatments have been used for many years, they are not always effective, and many patients relapse after initial treatment. Moreover, in some patients the response to therapy becomes weaker, or resistance to monotherapy develops over time. This is especially problematic for metastatic breast cancer or triple-negative breast cancer. Recently, combination therapies (in which two or more drugs are used to target two or more pathways) have emerged as promising new treatment options. Combination therapies are often more effective than monotherapies and demonstrate lower levels of toxicity during long-term treatment. In this review, we provide a comprehensive overview of current combination therapies, including molecular-targeted therapy, hormone therapy, immunotherapy, and chemotherapy. We also describe the molecular basis of breast cancer and the various treatment options for different breast cancer subtypes. While combination therapies are promising, we also discuss some of the challenges. Despite these challenges, the use of innovative combination therapy holds great promise compared with traditional monotherapies. In addition, the use of multidisciplinary technologies (such as nanotechnology and computer technology) has the potential to optimize combination therapies even further.

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Combining histone deacetylase inhibitors (HDACis) with other therapies for cancer therapy

Cited by 48 publications

References 168 publications

JMJD8 Is an M2 Macrophage Biomarker, and It Associates With DNA Damage Repair to Facilitate Stemness Maintenance, Chemoresistance, and Immunosuppression in Pan-Cancer

JMJD8 Is an M2 Macrophage Biomarker, and It Associates With DNA Damage Repair to Facilitate Stemness Maintenance, Chemoresistance, and Immunosuppression in Pan-Cancer

Polyphenols as Potent Epigenetics Agents for Cancer

Current Molecular Combination Therapies Used for the Treatment of Breast Cancer

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