About: Evaluating the efficacy of enzalutamide and the development of resistance in a preclinical mouse model of type-I endometrial carcinoma

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About: Evaluating the efficacy of enzalutamide and the development of resistance in a preclinical mouse model of type-I endometrial carcinoma Goto Sponge NotDistinct Permalink

An Entity of Type : schema:ScholarlyArticle, within Data Space : wasabi.inria.fr associated with source document(s)

Attributes	Values
type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
has title	Evaluating the efficacy of enzalutamide and the development of resistance in a preclinical mouse model of type-I endometrial carcinoma
Creator	Liu, Bei Leone, Gustavo Cohn, David Backes, J Bonala, Santosh Chamberlin, Helen Gallagher, James Goodfellow, Paul Koivisto, Christopher Nahhas, Georges Ngoi, Soo Parrish, Melodie Sanchez-Hodge, Rebekah Torres, Adrian Zeinner, Victor
Source	BioRxiv
abstract	Androgen Receptor (AR) signaling is a critical driver of hormone-dependent prostate cancer and has also been proposed to have biological activity in female hormone-dependent cancers, including type I endometrial carcinoma (EMC). In this study, we evaluated the preclinical efficacy of a third-generation AR antagonist, enzalutamide, in a genetic mouse model of EMC, Sprr2f-Cre;Ptenfl/fl. In this model, ablation of Pten in the uterine epithelium leads to localized and distant malignant disease as observed in human EMC. We hypothesized that administering enzalutamide through the diet would temporarily decrease the incidence of invasive and metastatic carcinoma, while prolonged administration would result in development of resistance and loss of efficacy. Short-term treatment with enzalutamide reduced overall tumor burden through increased apoptosis but failed to prevent progression of invasive and metastatic disease. These results suggest that AR signaling may have biphasic, oncogenic and tumor suppressive roles in EMC that are dependent on disease stage. Enzalutamide treatment increased Progesterone Receptor (PR) expression within both stromal and tumor cell compartments. Prolonged administration of enzalutamide decreased apoptosis, increased tumor burden and resulted in the clonal expansion of tumor cells expressing high levels of p53 protein, suggestive of acquired Trp53 mutations. In conclusion, we show that enzalutamide induces apoptosis in EMC but has limited efficacy overall as a single agent. Induction of PR, a negative regulator of endometrial proliferation, suggests that adding progestin therapy to enzalutamide administration may further decrease tumor burden and result in a prolonged response.
has issue date	2019-12-12(xsd:dateTime)
bibo:doi	10.1101/2019.12.06.868182
has license	biorxiv
sha1sum (hex)	c4cbd1688696aa74b7f732468c0333088d5a5ce4
schema:url	https://doi.org/10.1101/2019.12.06.868182
resource representing a document's title	Evaluating the efficacy of enzalutamide and the development of resistance in a preclinical mouse model of type-I endometrial carcinoma
schema:publication	bioRxiv
resource representing a document's body	covid:c4cbd1688696aa74b7f732468c0333088d5a5ce4#body_text
is schema:about of	named entity 'mutations' named entity 'EMC' named entity 'agent' named entity 'administration' named entity 'enzalutamide' named entity 'These' named entity 'dependent' named entity 'critical' named entity 'tumor' named entity 'hormone-dependent' named entity 'type-I' named entity 'biological activity' named entity 'reduced' named entity 'administration' named entity 'negative regulator' named entity 'hypothesized' named entity 'stromal' named entity 'high' named entity 'failed' named entity 'acquired' named entity 'suggestive' named entity 'result' named entity 'human' named entity 'burden' named entity 'Pten' named entity 'EMC' named entity 'clonal' named entity 'limited' named entity 'model' named entity 'enzalutamide' named entity 'resistance' named entity 'genetic mouse model' named entity 'apoptosis' named entity 'Androgen Receptor' named entity 'enzalutamide' named entity 'apoptosis' named entity 'enzalutamide' named entity 'metastatic disease' named entity 'enzalutamide' named entity 'biological activity' named entity 'oncogenic' named entity 'progestin' named entity 'epithelium' named entity 'ablation' named entity 'endometrial proliferation' named entity 'mice' named entity 'p53 protein' named entity 'endometrial' named entity 'ethanol' named entity 'leukocytes' named entity 'perirenal' named entity 'experimental design' named entity 'uterine' named entity 'MDSCs' named entity 'mice' named entity 'castration' named entity 'anti-androgen' named entity 'in-situ' named entity 'spleen' named entity 'castration-resistant prostate cancer' named entity 'upregulation' named entity 'uterus' named entity 'enzalutamide' named entity 'vagina' named entity 'estrous cycle' named entity 'endometrial carcinoma' named entity 'mice' named entity 'enzalutamide' named entity 'granulocytic' named entity 'tumors'

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