Novel Methods of Targeting IL-1 Signalling for the Treatment of Breast Cancer Bone Metastasis

Zhou, Jiaoyan; Down, Jennifer M.; George, Christopher N.; Murphy, Jessica; Lefley, Diane V.; Tulotta, Claudia; Alsharif, Marwa A.; Leach, Michael; Ottewell, Penelope D.

doi:10.3390/cancers14194816

Cited by 6 publications

(3 citation statements)

References 39 publications

(97 reference statements)

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“…Since widespread inflammation supports invasiveness as well as inhibits anti-tumor immune responses, IL-1 targeting has been thought to be a possible immunotherapeutic approach. Specifically, great interest has been given to IL-1β which is increased in several cancers and has proven to promote tumorigenesis, tumor invasiveness ( Zhou et al, 2022 ) and immunosuppression ( Krelin et al, 2007 ; Carmi et al, 2013 ; Voronov and Apte, 2020 ; Zhou et al, 2022 ).…”

Section: Immunosenescence Il-1 and Immune Checkpointmentioning

confidence: 99%

IL-1 and senescence: Friends and foe of EGFR neutralization and immunotherapy

Romaniello

Gelfo²,

Pagano³

et al. 2023

Front. Cell Dev. Biol.

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Historically, senescence has been considered a safe program in response to multiple stresses in which cells undergo irreversible growth arrest. This process is characterized by morphological and metabolic changes, heterochromatin formation, and secretion of inflammatory components, known as senescence-associated secretory phenotype (SASP). However, recent reports demonstrated that anti-cancer therapy itself can stimulate a senescence response in tumor cells, the so-called therapy-induced senescence (TIS), which may represent a temporary bypass pathway that promotes drug resistance. In this context, several studies have shown that EGFR blockage, by TKIs or moAbs, promotes TIS by increasing IL-1 cytokine production, thus pushing cells into a “pseudo-senescent” state. Today, senotherapeutic agents are emerging as a potential strategy in cancer treatment thanks to their dual role in annihilating senescent cells and simultaneously preventing their awakening into a resistant and aggressive form. Here, we summarize classic and recent findings about the cellular processes driving senescence and SASP, and we provide a state-of-the-art of the anti-cancer strategies available so far that exploits the activation and/or blockade of senescence-based mechanisms.

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Section: Immunosenescence Il-1 and Immune Checkpointmentioning

confidence: 99%

IL-1 and senescence: Friends and foe of EGFR neutralization and immunotherapy

Romaniello

Gelfo²,

Pagano³

et al. 2023

Front. Cell Dev. Biol.

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“…Polymeric micelles as drug carriers have been demonstrated to be promising in cancer chemotherapy and are already under clinical evaluation [12][13][14]. In our previous work [15], we synthesized polymeric micelles using Pluronic P123 (P123; polyoxyethylene-polyoxypropylenepolyoxyethylene triblock copolymer).…”

Section: Introductionmentioning

confidence: 99%

Dual ligand-targeted Pluronic P123 polymeric micelles enhance the therapeutic effect of breast cancer with bone metastases

GAO,

ZHANG,

KLEIJN

et al. 2024

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Bone metastasis secondary to breast cancer negatively impacts patient quality of life and survival. The treatment of bone metastases is challenging since many anticancer drugs are not effectively delivered to the bone to exert a therapeutic effect. To improve the treatment efficacy, we developed Pluronic P123 (P123)-based polymeric micelles dually decorated with alendronate (ALN) and cancer-specific phage protein DMPGTVLP (DP-8) for targeted drug delivery to breast cancer bone metastases. Doxorubicin (DOX) was selected as the anticancer drug and was encapsulated into the hydrophobic core of the micelles with a high drug loading capacity (3.44%). The DOX-loaded polymeric micelles were spherical, 123 nm in diameter on average, and exhibited a narrow size distribution. The in vitro experiments demonstrated that a pH decrease from 7.4 to 5.0 markedly accelerated DOX release. The micelles were well internalized by cultured breast cancer cells and the cell death rate of micelle-treated breast cancer cells was increased compared to that of free DOX-treated cells. Rapid binding of the micelles to hydroxyapatite (HA) microparticles indicated their high affinity for bone. P123-ALN/DP-8@DOX inhibited tumor growth and reduced bone resorption in a 3D cancer bone metastasis model. In vivo experiments using a breast cancer bone metastasis nude model demonstrated increased accumulation of the micelles in the tumor region and considerable antitumor activity with no organ-specific histological damage and minimal systemic toxicity. In conclusion, our study provided strong evidence that these pH-sensitive dual ligand-targeted polymeric micelles may be a successful treatment strategy for breast cancer bone metastasis.

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“…Inflammation is known as the “seventh hallmark of cancer” ( 15 – 17 ), and many studies have shown that inflammation plays an essential role in the development and progression of cancer ( 18 , 19 ), among which IL-1 is one of the classical inflammatory factors. Plays a vital role in the development of cancer ( 20 ). However, relatively few studies use IL-1 as a prognostic marker in lung adenocarcinoma.…”

Section: Introductionmentioning

confidence: 99%

Construction of IL-1 signalling pathway correlation model in lung adenocarcinoma and association with immune microenvironment prognosis and immunotherapy: Multi-data validation

Yang²,

Yu³

et al. 2023

Front. Immunol.

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Numerous studies have confirmed the inextricable link between inflammation and malignancy, which is also involved in developing lung adenocarcinoma, where IL-1 signalling is crucial. However, the predictive role of single gene biomarkers is insufficient, and more accurate prognostic models are needed. We downloaded data related to lung adenocarcinoma patients from the GDC, GEO, TISCH2 and TCGA databases for data analysis, model construction and differential gene expression analysis. The genes of IL-1 signalling-related factors were screened from published papers for subgroup typing and predictive correlation analysis. Five prognostic genes associated with IL-1 signalling were finally identified to construct prognostic prediction models. The K-M curves indicated that the prognostic models had significant predictive efficacy. Further immune infiltration scores showed that IL-1 signalling was mainly associated with enhanced immune cells, drug sensitivity of model genes was analysed using the GDSC database, and correlation of critical memories with cell subpopulation components was observed using single-cell analysis. In conclusion, we propose a predictive model based on IL-1 signalling-related factors, a non-invasive predictive approach for genomic characterisation, in predicting patients’ survival outcomes. The therapeutic response has shown satisfactory and effective performance. More interdisciplinary areas combining medicine and electronics will be explored in the future.

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Novel Methods of Targeting IL-1 Signalling for the Treatment of Breast Cancer Bone Metastasis

Cited by 6 publications

References 39 publications

IL-1 and senescence: Friends and foe of EGFR neutralization and immunotherapy

IL-1 and senescence: Friends and foe of EGFR neutralization and immunotherapy

Dual ligand-targeted Pluronic P123 polymeric micelles enhance the therapeutic effect of breast cancer with bone metastases

Construction of IL-1 signalling pathway correlation model in lung adenocarcinoma and association with immune microenvironment prognosis and immunotherapy: Multi-data validation

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