BET-Inhibitor I-BET762 and PARP-Inhibitor Talazoparib Synergy in Small Cell Lung Cancer Cells

Fiorentino, Francesco Paolo; Marchesi, Irene; Schröder, Christoph; Schmidt, Ronny; Yokota, Jun; Bagella, Luigi

doi:10.3390/ijms21249595

Cited by 26 publications

(27 citation statements)

References 77 publications

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“…Normalized Green Fluorescence Intensity (NGFI) of each spheroid, at each time point, was calculated as:

where GFI is green fluorescence integral at the analyzed time point, GFI 0 is green fluorescence integral of the same spheroid at time point zero (immediately after start of treatment), and A is the area of the same spheroid at the analyzed time point [ 81 , 82 ].…”

Section: Methodsmentioning

confidence: 99%

A Micro-Immunotherapy Sequential Medicine MIM-seq Displays Immunomodulatory Effects on Human Macrophages and Anti-Tumor Properties towards In Vitro 2D and 3D Models of Colon Carcinoma and in an In Vivo Subcutaneous Xenograft Colon Carcinoma Model

Jacques¹,

Marchesi²,

Fiorentino³

et al. 2022

IJMS

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In this study, the immunomodulatory effects of a sequential micro-immunotherapy medicine, referred as MIM-seq, were appraised in human primary M1 and M2 macrophages, in which the secretion of pro-inflammatory cytokines, such as interleukin (IL)-1β, IL-6, IL-12, IL-23, and tumor necrosis factor (TNF)-alpha, was inhibited. In addition, the potential anti-proliferative effects of MIM-seq on tumor cells was assessed in three models of colorectal cancer (CRC): an in vitro two-dimensions (2D) model of HCT-116 cells, an in vitro tri-dimensional (3D) model of spheroids, and an in vivo model of subcutaneous xenografted mice. In these models, MIM-seq displayed anti-proliferative effects when compared with the vehicle. In vivo, the tumor growth was slightly reduced in MIM-seq-treated animals. Moreover, MIM-seq could slightly reduce the growth of our spheroid models, especially under serum-deprivation. When MIM-seq was combined with two well-known anti-cancerogenic agents, either resveratrol or etoposide, MIM-seq could even further reduce the spheroid’s volume, pointing up the need to further assess whether MIM-seq could be beneficial for CRC patients as an adjuvant therapy. Altogether, these data suggest that MIM-seq could have anti-tumor properties against CRC and an immunomodulatory effect towards the mediators of inflammation, whose systemic dysregulation is considered to be a poor prognosis for patients.

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“…Normalized Green Fluorescence Intensity (NGFI) of each spheroid, at each time point, was calculated as:

Section: Methodsmentioning

confidence: 99%

A Micro-Immunotherapy Sequential Medicine MIM-seq Displays Immunomodulatory Effects on Human Macrophages and Anti-Tumor Properties towards In Vitro 2D and 3D Models of Colon Carcinoma and in an In Vivo Subcutaneous Xenograft Colon Carcinoma Model

Jacques¹,

Marchesi²,

Fiorentino³

et al. 2022

IJMS

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“…Although research on BET inhibitors is still a research focus, the combination use of BET inhibitors with other drugs is also being explored. BET inhibitors can be used in combination with other types of inhibitors in order to promote the therapeutic effect or reduce adverse reactions ( 283 ). For example, the combination of BET inhibitor I-BET762 and PARP inhibitor Talazoparib Synergy is used in the treatment of SCLC and has a synergistic effect ( 283 ).…”

Section: Acetylation System-based Targeted Drugs In Cancermentioning

confidence: 99%

The role of protein acetylation in carcinogenesis and targeted drug discovery

2022

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Protein acetylation is a reversible post-translational modification, and is involved in many biological processes in cells, such as transcriptional regulation, DNA damage repair, and energy metabolism, which is an important molecular event and is associated with a wide range of diseases such as cancers. Protein acetylation is dynamically regulated by histone acetyltransferases (HATs) and histone deacetylases (HDACs) in homeostasis. The abnormal acetylation level might lead to the occurrence and deterioration of a cancer, and is closely related to various pathophysiological characteristics of a cancer, such as malignant phenotypes, and promotes cancer cells to adapt to tumor microenvironment. Therapeutic modalities targeting protein acetylation are a potential therapeutic strategy. This article discussed the roles of protein acetylation in tumor pathology and therapeutic drugs targeting protein acetylation, which offers the contributions of protein acetylation in clarification of carcinogenesis, and discovery of therapeutic drugs for cancers, and lays the foundation for precision medicine in oncology.

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“…In addition to their role in blocking androgen receptor signalling, BET inhibitors promote apoptosis, induce DNA damage, and impair DNA repair [70–72]. Thus, BET inhibitors have been combined with PARPiin various tumour types [73–76]. A phase II clinical trial combining ZEN003694 and the PARPi talazoparib, in patients with triple negative breast cancer, is projected to conclude in early 2024 (NCT03901469) (Fig.…”

Section: New Inhibitors Targeting the Epigenomementioning

confidence: 99%

New approaches to targeting epigenetic regulation in prostate cancer

Thompson

Choo

Bolton

et al. 2022

Current Opinion in Urology

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Purpose of reviewMany clinical trials are currently underway to target the epigenome of castration-resistant prostate cancer. In this review, we summarize the major epigenetic alterations that occur during prostate cancer progression, describe their biological consequences, and highlight potential of therapies that target epigenetic regulators for use in patients.Recent findingsEpigenetic alterations frequently occur in tumour suppressor genes, DNA repair genes, and genes that regulate cell proliferation and differentiation. Unlike genetic alterations, epigenetic changes are reversible, making them promising targets for cancer therapy. Epigenetic regulators can be divided into three broad groups: writers, readers, and erasers, each with specific drug targets that are being assessed in phase I and II clinical trials for prostate cancer. CBP/p300, and BRD4 are coregulators of the androgen receptor and inhibit androgen signalling, making bromodomain extra-terminal inhibitors and CBP/p300 inhibitors attractive targets in prostate cancer. Enhancer of zeste homolog 2, a histone methyltransferase, is also a potential target in castrate-resistant prostate cancer. An emerging direction is to combine epigenetic inhibitors with other compounds to enhance their efficacy.SummaryPreclinical studies indicate that the epigenome is a potential target in prostate cancer, and clinical trials are testing multiple agents that target the epigenome in different ways. However, the process of translating these therapies into the clinic is ongoing and none have yet been approved for castrate-resistant prostate cancer.

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BET-Inhibitor I-BET762 and PARP-Inhibitor Talazoparib Synergy in Small Cell Lung Cancer Cells

Cited by 26 publications

References 77 publications

A Micro-Immunotherapy Sequential Medicine MIM-seq Displays Immunomodulatory Effects on Human Macrophages and Anti-Tumor Properties towards In Vitro 2D and 3D Models of Colon Carcinoma and in an In Vivo Subcutaneous Xenograft Colon Carcinoma Model

A Micro-Immunotherapy Sequential Medicine MIM-seq Displays Immunomodulatory Effects on Human Macrophages and Anti-Tumor Properties towards In Vitro 2D and 3D Models of Colon Carcinoma and in an In Vivo Subcutaneous Xenograft Colon Carcinoma Model

The role of protein acetylation in carcinogenesis and targeted drug discovery

New approaches to targeting epigenetic regulation in prostate cancer

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