Abstract 1062: Antiproliferative activity of EC359, an inhibitor of leukemia inhibitory factor receptor (LIF-R), singly and in combination with chemotherapy drugs against pancreatic cancer cell lines
Notice bibliographique
Résumé
Abstract Although combination chemotherapy treatments such as FOLFIRINOX (5-fluorouracil, oxaliplatin, irinotecan), gem-abraxane (gemcitabine and nab-paclitaxel) and GTX (gemcitabine, docetaxel and capecitabine) have improved survival of pancreatic cancer patients incrementally, 5-year-survival for this disease remains dismal. New and more effective treatments are needed. Pancreatic stellate cells (PSCs), a form of fibroblasts that comprise much of the pancreatic tumor microenvironment, interact with the cancer cells via the cytokine leukemia inhibitory factor (LIF) and its receptor, LIF-R. This interaction contributes to tumor progression, survival, and resistance to various therapies, and is an important target for novel therapy. A small molecule inhibitor of LIF-R, EC359, inhibits growth of breast cancer cell line tumor explants in mice (Mol Cancer Ther 18: 1341-1354, 2019) and potentially modulates the activity of gemcitabine against such explants (Genes Cancer 10: 1-10, 2019). Given the involvement of the LIF axis in pancreatic cancer, EC359 was tested for its ability to inhibit proliferation of the human pancreatic cancer cell lines PANC-1, Capan-1, and Capan-2, and its possible influence on activity of chemotherapy drugs against these cell lines. Five-day drug exposures were conducted in 96-well plates. Relative cell density determined using vital stains (alamarBlue©, neutral red) was reported as a percent of the fluorescence/absorbance of control cultures. The 3 cell lines exhibited different sensitivities to EC359, with IC50 values ranging from 5 nM (Capan-1) to 150 nM (Capan-2). When combined with anti-pancreatic cancer standard-of-care drugs, EC359 yielded synergistic interactions in a concentration-dependent manner. Depending on the cell line, EC359 decreased the IC50 value for oxaliplatin by as much as 83%. Such enhancements of cytotoxicity for other drugs were up to 84% for docetaxel, 67% for paclitaxel, and 50% for irinotecan. EC359 was also synergistic with IBR120 (a novel small molecule inhibitor of RAD51) against PANC-1 cells. EC359 additively inhibited proliferation in combination with irinotecan or 5-FUdR. The nanomolar activity of EC359 against pancreatic cancer cell lines makes it a good candidate for potential treatment of this generally refractory disease. The synergistic interaction of EC359 with standard-of-care drugs provides an opportunity for increasing the therapeutic index for these agents, and ultimately improving clinical outcomes for pancreatic cancer and other cancers against which EC359 is currently in clinical trial. Citation Format: Peter J. Ferguson, Hareesh Nair, Mark D. Vincent, James Koropatnick. Antiproliferative activity of EC359, an inhibitor of leukemia inhibitory factor receptor (LIF-R), singly and in combination with chemotherapy drugs against pancreatic cancer cell lines [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1062.
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 | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| 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 ».