Combined cetuximab and trastuzumab are superior to gemcitabine in the treatment of human pancreatic carcinoma xenografts

Autor: Caroline Bascoul-Mollevi, Alexandre Ho-Pun-Cheung, Bruno Robert, Frédérique Penault-Llorca, Christelle Larbouret, Isabelle Navarro-Teulon, Jean-Pierre Mach, David Azria, André Pèlegrin, Sébastien Morisseau
Přispěvatelé: Le Ster, Yves, Institut de recherche en cancérologie de Montpellier (IRCM - U896 Inserm - UM1), Université Montpellier 1 (UM1)-CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), CRLC Val d'Aurelle-Paul Lamarque, CRLCC Val d'Aurelle - Paul Lamarque, Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), UNICANCER, Département de biochimie, Université de Lausanne = University of Lausanne (UNIL), CRLCC Val d'Aurelle - Paul Lamarque-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 1 (UM1), Université de Lausanne (UNIL)
Jazyk: angličtina
Rok vydání: 2017
Předmět:
Pancreatic disease
Receptor
ErbB-2
Cetuximab
Deoxycytidine
MESH: Antibodies
Monoclonal
Mice
0302 clinical medicine
Trastuzumab
Antineoplastic Combined Chemotherapy Protocols
MESH: Animals
Epidermal growth factor receptor
0303 health sciences
biology
gemcitabine
Antibodies
Monoclonal
Hematology
Immunohistochemistry
3. Good health
ErbB Receptors
MESH: Antineoplastic Combined Chemotherapy Protocols
Oncology
MESH: Receptor
erbB-2
030220 oncology & carcinogenesis
[SDV.IMM]Life Sciences [q-bio]/Immunology
Female
CA19-9
monoclonal antibodies
MESH: Pancreatic Neoplasms
medicine.drug
MESH: Xenograft Model Antitumor Assays
MESH: Cell Line
Tumor
[SDV.IMM] Life Sciences [q-bio]/Immunology
EGFR
Blotting
Western
HER2
pancreatic carcinoma
Mice
Nude
[SDV.CAN]Life Sciences [q-bio]/Cancer
MESH: Receptor
Epidermal Growth Factor
Antibodies
Monoclonal
Humanized
Article
03 medical and health sciences
[SDV.CAN] Life Sciences [q-bio]/Cancer
Cell Line
Tumor
Pancreatic cancer
medicine
MESH: Mice
Nude
Animals
Humans
MESH: Blotting
Western
MESH: Mice
030304 developmental biology
MESH: Humans
business.industry
MESH: Deoxycytidine
Cancer
MESH: Immunohistochemistry
[SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology
medicine.disease
Xenograft Model Antitumor Assays
Gemcitabine
[SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology
Pancreatic Neoplasms
MESH: Antibodies
Monoclonal
Humanized
Cancer research
biology.protein
business
MESH: Female
Zdroj: Annals of Oncology
Annals of Oncology, Elsevier, 2010, 21 (1), pp.98-103. ⟨10.1093/annonc/mdp496⟩
Annals of Oncology, vol. 21, no. 1, pp. 98-103
ISSN: 0923-7534
1569-8041
DOI: 10.1093/annonc/mdp496⟩
Popis: International audience; BACKGROUND: Pancreatic carcinoma remains a treatment-refractory cancer with a poor prognosis. Here, we compared anti-epidermal growth factor receptor (EGFR) and anti-HER2 monoclonal antibodies (2mAbs) injections with standard gemcitabine treatment on human pancreatic carcinoma xenografts. MATERIALS AND METHODS: Nude mice, bearing human pancreatic carcinoma xenografts, were treated with either combined anti-EGFR (cetuximab) and anti-HER2 (trastuzumab) or gemcitabine, and tumor growth was observed. RESULTS AND CONCLUSION: In first-line therapy, mice survival was significantly longer in the 2mAbs group compared with gemcitabine (P < 0.0001 for BxPC-3, P = 0.0679 for MiaPaCa-2 and P = 0.0019 for Capan-1) and with controls (P < 0.0001). In second-line therapy, tumor regressions were observed after replacing gemcitabine by 2mAbs treatment, resulting in significantly longer animal survival compared with mice receiving continuous gemcitabine injections (P = 0.008 for BxPC-3, P = 0.05 for MiaPaCa-2 and P < 0.001 for Capan-1). Therapeutic benefit of 2mAbs was observed despite K-Ras mutation. Interestingly, concerning the mechanism of action, coinjection of F(ab')(2) fragments from 2mAbs induced significant tumor growth inhibition, compared with controls (P = 0.001), indicating that the 2mAbs had an Fc fragment-independent direct action on tumor cells. This preclinical study demonstrated a significant improvement of survival and tumor regression in mice treated with anti-EGFR/anti-HER2 2mAbs in first- and second-line treatments, compared with gemcitabine, independently of the K-Ras status.
Databáze: OpenAIRE
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