Development of an adverse outcome pathway network for breast cancer: a comprehensive representation of the pathogenesis, complexity and diversity of the disease

Del’haye, Gigly G.; Nulmans, Ine; Bouteille, Sandrine P.; Sermon, Karolien; Wellekens, Brecht; Rombaut, Matthias; Vanhaecke, Tamara; Heyden, Yvan Vander; Kock, Joery De

doi:10.1007/s00204-022-03351-w

Cited by 8 publications

(4 citation statements)

References 77 publications

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“…A partial AOP for decreased gonadotropin-releasing hormone (GnRH) expression in hypothalamus leading to reduced testosterone production has been postulated ( Lu et al, 2023 ). There are also published putative AOPs for female reproductive toxicity, including disrupted folliculogenesis and follicle maturation, decreased ovulation, disrupted puberty onset in girls, uterine tumours, and breast cancer causally linked to disrupted hypothalamic–pituitary–gonadal (HPG) axis signalling, ER activation, estrogen metabolism, and aromatase inhibition ( Del’haye et al, 2022 ; Franssen et al, 2022 ; Hernandez-Jerez et al, 2023 ; Johansson et al, 2020 ; Myden et al, 2022 ; Wikoff et al, 2016 ). Apart from the challenge of finding AOPs published in the literature, such AOPs cannot be included in the AOPN using the computational automated process and must be manually added.…”

Section: Discussionmentioning

confidence: 99%

Building an adverse outcome pathway network for estrogen-, androgen- and steroidogenesis-mediated reproductive toxicity

Zilliacus,

Draskau,

Johansson

et al. 2024

Front. Toxicol.

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Introduction: Adverse Outcome Pathways (AOPs) can support both testing and assessment of endocrine disruptors (EDs). There is, however, a need for further development of the AOP framework to improve its applicability in a regulatory context. Here we have inventoried the AOP-wiki to identify all existing AOPs related to mammalian reproductive toxicity arising from disruption to the estrogen, androgen, and steroidogenesis modalities. Core key events (KEs) shared between relevant AOPs were also identified to aid in further AOP network (AOPN) development.Methods: A systematic approach using two different methods was applied to screen and search the entire AOP-wiki library. An AOPN was visualized using Cytoscape. Manual refinement was performed to remove AOPS devoid of any KEs and/or KERs.Results: Fifty-eight AOPs relevant for mammalian reproductive toxicity were originally identified, with 42 AOPs included in the final AOPN. Several of the KEs and KE relationships (KERs) described similar events and were thus merged to optimize AOPN construction. Sixteen sub-networks related to effects on hormone levels or hormone activity, cancer outcomes, male and female reproductive systems, and overall effects on fertility and reproduction were identified within the AOPN. Twenty-six KEs and 11 KERs were identified as core blocks of knowledge in the AOPN, of which 19 core KEs are already included as parameters in current OECD and US EPA test guidelines.Discussion: The AOPN highlights knowledge gaps that can be targeted for further development of a more complete AOPN that can support the identification and assessment of EDs.

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Section: Discussionmentioning

confidence: 99%

Building an adverse outcome pathway network for estrogen-, androgen- and steroidogenesis-mediated reproductive toxicity

Zilliacus,

Draskau,

Johansson

et al. 2024

Front. Toxicol.

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“…When comparing BC patients to healthy subjects, researchers discovered increased miR-21 expression in their serum. It was found to be more abundant in primary breast cancer tissues and breast cancer cell lines [42,43].…”

Section: Breast Cancer and Micro-rnasmentioning

confidence: 99%

MiRNAs as Promising Therapeutic Targets for Breast Cancer

Fakhry,

Abdel-Hamed,

Mesbah

et al. 2024

OBM Genet

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Breast cancer (BC) is the most common cause of cancer-related death and is the malignancy most frequently diagnosed in females worldwide. BC incidence is predicted to continue increasing worldwide. Without interventions, annual new cases will reach over 3 million by 2030. Genetic abnormalities account for almost 70% of all BC cases worldwide. Biological pathways implicated include non-coding RNAs (ncRNAs). MiRNAs are small non-coding RNA molecules that play a role in post-transcriptional regulation of gene expression. They can function as either tumor suppressors or oncogenes, and their role depends on the specific miRNA and target genes affected. The research on miRNA-based cancer treatments has yielded promising results. Depending on recent data, the goal of this review was to summarize the mechanisms that explain the role of some miRNAs in BC pathogenesis and drug resistance. However, highlighting the areas needing further exploration and more research is required before using microRNAs in clinical settings.

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“…Therefore, to assess inorganic cadmium-induced toxicity, it is imperative to construct an AOP network specific to cadmium and its inorganic compounds. Till date, AOP-Wiki has been leveraged to build over 32 different AOP networks for a variety of adverse outcomes such as reproductive disorders [30][31][32][33], neurologic disorders [34][35][36][37], endocrine disorders [25,[38][39][40][41][42][43], developmental disorders [30,40,44,45], hepatic disorders [25,46,47], pulmonary disorders [48][49][50], and others [26,27,[51][52][53][54][55][56][57][58]. Importantly, Chai et al [33] had integrated the data within Comparative Toxicogenomics Database (CTD) [59] and AOP-Wiki to construct an AOP network specific to arsenic-induced reproductive toxicity.…”

Section: Introductionmentioning

confidence: 99%

An integrative data-centric approach to derivation and characterization of an adverse outcome pathway network for cadmium-induced toxicity

Sahoo,

Chivukula,

Ramesh

et al. 2024

Science of The Total Environment

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Development of an adverse outcome pathway network for breast cancer: a comprehensive representation of the pathogenesis, complexity and diversity of the disease

Abstract: with details of the nature of the infringement. We will investigate the claim and if justified, we will take the appropriate steps.

Cited by 8 publications

References 77 publications

Building an adverse outcome pathway network for estrogen-, androgen- and steroidogenesis-mediated reproductive toxicity

Building an adverse outcome pathway network for estrogen-, androgen- and steroidogenesis-mediated reproductive toxicity

MiRNAs as Promising Therapeutic Targets for Breast Cancer

An integrative data-centric approach to derivation and characterization of an adverse outcome pathway network for cadmium-induced toxicity

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