Anti-tumoral activity of the Pan-HER (Sym013) antibody mixture in gemcitabine-resistant pancreatic cancer models.
Animals
Antibodies
/ pharmacology
Antimetabolites, Antineoplastic
/ pharmacology
Cell Line, Tumor
Cell Proliferation
/ drug effects
Deoxycytidine
/ analogs & derivatives
Drug Resistance, Neoplasm
ErbB Receptors
/ antagonists & inhibitors
Female
Humans
Mice, Nude
Pancreatic Neoplasms
/ drug therapy
Receptor, ErbB-2
/ antagonists & inhibitors
Receptor, ErbB-3
/ antagonists & inhibitors
Tumor Burden
/ drug effects
Xenograft Model Antitumor Assays
Gemcitabine
EGFR
HER2
HER3
Pan-Her
chemoresistance
gemcitabine
pancreatic cancer
Journal
mAbs
ISSN: 1942-0870
Titre abrégé: MAbs
Pays: United States
ID NLM: 101479829
Informations de publication
Date de publication:
Historique:
entrez:
20
4
2021
pubmed:
21
4
2021
medline:
20
1
2022
Statut:
ppublish
Résumé
Chemoresistance, particularly to gemcitabine, is a major challenge in pancreatic cancer. The epidermal growth factor receptor (EGFR) and human epidermal growth factor receptors 2 and 3 (HER2, HER3) are expressed in many tumors, and they are relevant therapeutic targets due to their synergistic interaction to promote tumor aggressiveness and therapeutic resistance. Cocktails of antibodies directed against different targets are a promising strategy to overcome these processes. Here, we found by immunohistochemistry that these three receptors were co-expressed in 11% of patients with pancreatic adenocarcinoma. We then developed gemcitabine-resistant pancreatic cancer cell models (SW-1990-GR and BxPC3-GR) and one patient-derived xenograft (PDX2846-GR) by successive exposure to increasing doses of gemcitabine. We showed that expression of EGFR, HER2 and HER3 was increased in these gemcitabine-resistant pancreatic cancer models, and that an antibody mixture against all three receptors inhibited tumor growth in mice and downregulated HER receptors. Finally, we demonstrated that the Pan-HER and gemcitabine combination has an additive effect
Identifiants
pubmed: 33876707
doi: 10.1080/19420862.2021.1914883
pmc: PMC8078530
doi:
Substances chimiques
Antibodies
0
Antimetabolites, Antineoplastic
0
Deoxycytidine
0W860991D6
EGFR protein, human
EC 2.7.10.1
ERBB2 protein, human
EC 2.7.10.1
ERBB3 protein, human
EC 2.7.10.1
ErbB Receptors
EC 2.7.10.1
Receptor, ErbB-2
EC 2.7.10.1
Receptor, ErbB-3
EC 2.7.10.1
Gemcitabine
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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