The role of CUDC‐907, a dual phosphoinositide‐3 kinase and histone deacetylase inhibitor, in inhibiting proliferation of adult T‐cell leukemia

Ishikawa, Chie; Mori, Nozomu

doi:10.1111/ejh.13508

Cited by 8 publications

(2 citation statements)

References 50 publications

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“…It was found to exert a cytotoxic effect in HTLV-1-infected cells by inhibiting the phosphorylation of downstream PI3K targets, such as AKT, REL A, and p70 S6K, and by decreasing HSP90 chaperone activity in ATL cells in vitro. Moreover, in HTLV-1-infected cells, CUDC-907 induced the upregulation of caspases, concomitant with the down-regulation of antiapoptotic gene expression and the suppression of NF-κB activation by inhibiting IKKα/ß phosphorylation [92]. The suppression of NF-κB signaling proved to be one of the most important means to counteract the growth of HTLV-1-infected cells.…”

Section: Proposals For Htlv-1/atl-targeted Therapymentioning

confidence: 98%

Human T-Cell Leukemia Virus Type 1 Oncogenesis between Active Expression and Latency: A Possible Source for the Development of Therapeutic Targets

Marino-Merlo,

Grelli,

Mastino

et al. 2023

IJMS

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The human T-cell leukemia virus type 1 (HTLV-1) is the only known human oncogenic retrovirus. HTLV-1 can cause a type of cancer called adult T-cell leukemia/lymphoma (ATL). The virus is transmitted through the body fluids of infected individuals, primarily breast milk, blood, and semen. At least 5–10 million people in the world are infected with HTLV-1. In addition to ATL, HTLV-1 infection can also cause HTLV-I-associated myelopathy (HAM/TSP). ATL is characterized by a low viral expression and poor prognosis. The oncogenic mechanism triggered by HTLV-1 is extremely complex and the molecular pathways are not fully understood. However, viral regulatory proteins Tax and HTLV-1 bZIP factor (HBZ) have been shown to play key roles in the transformation of HTLV-1-infected T cells. Moreover, several studies have shown that the final fate of HTLV-1-infected transformed Tcell clones is the result of a complex interplay of HTLV-1 oncogenic protein expression with cellular transcription factors that subvert the cell cycle and disrupt regulated cell death, thereby exerting their transforming effects. This review provides updated information on the mechanisms underlying the transforming action of HTLV-1 and highlights potential therapeutic targets to combat ATL.

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Section: Proposals For Htlv-1/atl-targeted Therapymentioning

confidence: 98%

Human T-Cell Leukemia Virus Type 1 Oncogenesis between Active Expression and Latency: A Possible Source for the Development of Therapeutic Targets

Marino-Merlo,

Grelli,

Mastino

et al. 2023

IJMS

View full text Add to dashboard Cite

show abstract

“…The molecule was further taken into phase 1a/1b clinical trials against head and neck squamous cell carcinoma and was found to be well tolerated. Another dual inhibitor CUDC-907 (PI3K/HDAC dual inhibitor) was developed and it was tested against different solid cancers like lung and esophageal cancer, neuroblastoma, and also in T-cell leukemia. − …”

Section: Newer Approaches In Epigenetic Therapymentioning

confidence: 99%

Advances in the Delivery and Development of Epigenetic Therapeutics for the Treatment of Cancer

Ghosh,

Himaja,

Biswas

et al. 2023

Mol. Pharmaceutics

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Gene expression at the transcriptional level is altered by epigenetic modifications such as DNA methylation, histone methylation, and acetylation, which can upregulate, downregulate, or entirely silence genes. Pathological dysregulation of epigenetic processes can result in the development of cancer, neurological problems, metabolic disorders, and cardiovascular diseases. It is of promising therapeutic interest to find medications that target these epigenetic alterations. Despite the enormous amount of work that has been done in this area, very few molecules have been approved for clinical purposes. This article provides a comprehensive review of recent advances in epigenetic therapeutics for cancer, with a specific focus on emerging delivery and development strategies. Various delivery systems, including prodrugs, conjugated molecules, nanoparticles (NPs), and liposomes, as well as remedial strategies such as combination therapies, and epigenetic editing, are being investigated to improve the efficacy and specificity of epigenetic drugs (epi-drugs). Furthermore, the challenges associated with available epi-drugs and the limitations of their translation into clinics have been discussed. Target selection, isoform selectivity, physiochemical properties of synthesized molecules, drug screening, and scalability of epi-drugs from preclinical to clinical fields are the major shortcomings that are addressed. This Review discusses novel strategies for the identification of new biomarkers, exploration of the medicinal chemistry of epigenetic modifiers, optimization of the dosage regimen, and design of proper clinical trials that will lead to better utilization of epigenetic modifiers over conventional therapies. The integration of these approaches holds great potential for improving the efficacy and precision of epigenetic treatments, ultimately benefiting cancer patients.

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The pathogenesis and development of targeted drugs in acute T lymphoblastic leukaemia

Chen

Xin

Wei

et al. 2023

British J Pharmacology

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Acute lymphoblastic leukaemia (ALL) is mainly classified into acute T-and Blymphoblastic leukaemia according to the source of its lymphocytes, thymus and bone. Among them, the incidence of adult T-cell accounts for about 25% of adult acute lymphoblastic leukaemia, but the degree of malignancy is high and the treatment rate and prognosis are poor. At this stage, there are few targeted drugs and the commonly used broad-spectrum chemotherapeutic drugs have poor efficacy and many adverse drug reactions. Understanding and investigating the pathogenesis of T-acute lymphoblastic leukaemia is very important for further developing new targeting drugs and improving existing drugs. Dysregulated signalling pathways are the main aetiological factors of T-acute lymphoblastic leukaemia. They play crucial roles in promoting tumour initiation, progression, drug design and therapy responses. This is primarily because signalling pathways are indispensable for many cellular biological processes, including tumour growth, migration, invasion, metastasis and others. As a result, small molecule inhibitors targeting the major kinase components of the signalling pathway have received a lot of attention and have been developed and evaluated in preclinical models and clinical trials. Already marketed drugs are also being repurposed in combination therapies to further improve efficacy and overcome tumour cell resistance. In this review, we have aimed to examine the latest and most classical signalling pathways in the aetiology of T-acute lymphoblastic leukaemia and shed light on potential targets for novel therapeutic agents to act on.

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The role of CUDC‐907, a dual phosphoinositide‐3 kinase and histone deacetylase inhibitor, in inhibiting proliferation of adult T‐cell leukemia

Cited by 8 publications

References 50 publications

Human T-Cell Leukemia Virus Type 1 Oncogenesis between Active Expression and Latency: A Possible Source for the Development of Therapeutic Targets

Human T-Cell Leukemia Virus Type 1 Oncogenesis between Active Expression and Latency: A Possible Source for the Development of Therapeutic Targets

Advances in the Delivery and Development of Epigenetic Therapeutics for the Treatment of Cancer

The pathogenesis and development of targeted drugs in acute T lymphoblastic leukaemia

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