Abstract A041: Targeting EGFR reverses paclitaxel resistance associated with ABCB1 overexpression in triple-negative breast cancer
Notice bibliographique
Résumé
Abstract Background: Breast cancer represents a heterogeneous group of tumors that exhibit a wide spectrum of clinical, pathologic, and molecular features. Of these tumors, triple-negative breast cancer (TNBCs), shows one of the most aggressive clinical behaviors with distinctive metastatic patterns and very poor prognosis. TNBC is characterized by the absence of expression of estrogen receptor, progesterone receptor, and low levels of human epidermal growth factor (HER2). Paclitaxel (PTX) is among the most effective anti-cancer agents developed in the past decades, which is widely used in the treatment of patients with locally advanced and metastatic breast cancer. TNBCs are initially highly responsive to PTX however; the majorities of TNBC patients acquire resistance and develop progressive disease. Therefore, acquired resistance to paclitaxel has become one of the major obstacles in the successful treatment of patients with TNBC. Several mechanisms of resistance to paclitaxel has been identified, however there is little data about mechanisms of resistance to chemotherapy in TNBCs. Methods: In order to investigate the molecular mechanisms of acquired resistance to PTX in TNBCs, we developed four resistant TNBC cell lines (BT20, SUM149, MA-MB-231 and MDA-MB-436) by exposure of cells to increasing concentrations of PTX. We used an integrative analysis of array CGH and gene expression data to gain insights into the interplay of functional changes of the genome in TNBC resistant cell lines. Results: We found a novel amplification of the ABCB1 gene in BT20 and SUM149 resistant cell lines only. Gene expression analysis revealed significant up-regulation of expression of ABCB1 and EGFR ligands in SUM149 and BT20 resistant cells compared to parental cell lines. The functional activity of ABC transporters assessed using Rhodamine 123 efflux assay demonstrated a marked increase in the efflux of rhodamine in SUM149-R and BT20-R, which was reversed by verapamil. We treated resistant cells with two anti-EGFR drugs, lapatinib and neratinib, which are also known ABC transporter inhibitors, and found that both drugs inhibited rhodamine 123 efflux and restored sensitivity to PTX in these PTX-resistant TNBC cells. Conclusion: This is the first report of ABCB1 gene amplification in paclitaxel resistant triple negative breast cancer cells. Our results suggest that ABCB1 gene amplification and EGFR ligand over-expression plays a critical role in the development of PTX resistance in TNBC cells, and that this resistance can be targeted by therapy with anti-EGFR agents. Thus, ABCB1 gene amplification and EGFR ligand expression may be novel predictive biomarkers for both chemotherapy and anti-EGFR therapy in TNBCs. Citation Format: Elaheh Ahmadzadeh, Ewa Przybytkowski, Adriana Aguilar-Mahecha, Mark Basik. Targeting EGFR reverses paclitaxel resistance associated with ABCB1 overexpression in triple-negative breast cancer. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Breast Cancer Research: Genetics, Biology, and Clinical Applications; Oct 3-6, 2013; San Diego, CA. Philadelphia (PA): AACR; Mol Cancer Res 2013;11(10 Suppl):Abstract nr A041.
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) | 0,001 | 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) | 0,002 | 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 ».