Abstract 224: Methyl-CpG-binding domain protein 2 (Mbd2) as a therapeutic target in breast cancer
Notice bibliographique
Résumé
Abstract Abnormal DNA methylation is frequently observed in the cancer epigenome, rendering it a prime target for pharmacological manipulation. Methyl-CpG-binding domain protein 2 (Mbd2), a reader of DNA methylation, has been shown to be strongly linked to various malignancies, including breast cancer, establishing Mbd2 as a viable and effective therapeutic target. Our previous studies have demonstrated that genetic deletion of Mbd2 significantly reduces primary breast tumor growth and lung metastasis in a well-established transgenic mouse model of breast cancer. In the current study, we examined the effect of pharmacological inhibition of Mbd2 on breast cancer progression and metastasis to non skeletal and skeletal sites. Several small-molecule inhibitors for Mbd2 have been described, and among these, KCC-07 was shown to significantly reduce medulloblastoma in vitro and in vivo. Treatment of mouse luminal B breast cancer cell lines (PyMT-R221A, E0071) with KCC-07 resulted in a time- and dose-dependent decrease in tumor cell proliferation and reduced the invasiveness of the cells in vitro. These results were recapitulated in vivo, where PyMT-R221A cells inoculated via mammary fat pad (m.f.p) and intra-tibial (i.t) routes into female FVB mice and treated with vehicle alone or KCC-07 (100.0 mg/kg) 3QW via the intraperitoneal route for three weeks showed a decrease in tumor volume and skeletal metastasis. Further immunohistochemical analyses of the tumor tissues using markers of tumor proliferation (Ki67), angiogenesis (CD31), and bone resorption (TRAP), as well as any potential side effects on animal toxicity and global transcriptomic changes of the PyMT-R221A cells induced by treatment with KCC-07, will be presented and discussed. In other studies, PyMT-R221A cells were treated with the most effective dose of Mbd2 siRNA and KCC-07 (40µM) and cellular RNA from control and experimental groups was extracted and subjected to RNA-seq analysis, which is now being analyzed and validated in depth. Results from these analyses will identify key Mbd2-mediated signaling pathways and genes that play an important role in breast cancer. Taken together, the results of this study will provide mechanistic insights into the therapeutic potential of targeting Mbd2 with KCC-07 to block breast cancer growth and metastasis in a preclinical setting. These findings could be highly valuable for the future evaluation of selective inhibitors of Mbd2 to treat breast cancer patients. Citation Format: Olivia Dumas, Niaz Mahmood, Ani Arakelian, Moshe Szyf, Shafaat Rabbani. Methyl-CpG-binding domain protein 2 (Mbd2) as a therapeutic target in breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 224.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,001 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,001 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,001 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».