Prioritization of EGFR/IGF-IR/VEGFR2 combination targeted therapies utilizing cancer models.
Anticancer Res
; 29(6): 1999-2007, 2009 Jun.
Article
in En
| MEDLINE
| ID: mdl-19528458
ABSTRACT
BACKGROUND:
Rational strategies utilizing anticancer efficacy and biological principles are needed for the prioritization of specific combination targeted therapy approaches for clinical development, from among the many with experimental support. MATERIALS ANDMETHODS:
Antibodies targeting epidermal growth factor receptor (EGFR) (cetuximab), insulin-like growth factor-1 receptor (IGF-IR) (IMC-A12) or vascular endothelial growth factor receptor 2 (VEGFR2) (DC101), were dosed alone or in combination, in 11 human tumor xenograft models established in mice. Efficacy readouts included the tumor burden and incidence of metastasis, as well as tumor active hypoxia inducible factor-1 (HIF-1), human VEGF and blood vessel density.RESULTS:
Cetuximab and DC101 contributed potent and non-overlapping benefits to the combination approach. Moreover, DC101 prevented escape from IMC-A12 + cetuximab in a colorectal cancer model and cetuximab prevented escape from DC101 therapy in a pancreatic cancer model.CONCLUSION:
Targeting VEGFR2 + EGFR was prioritized over other treatment strategies utilizing EGFR, IGF-IR and VEGFR2 antibodies. The criteria that proved to be valuable were a non-overlapping spectrum of anticancer activity and the prevention of resistance to another therapy in the combination.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Pancreatic Neoplasms
/
Colorectal Neoplasms
/
Receptor, IGF Type 1
/
Vascular Endothelial Growth Factor Receptor-2
/
Disease Models, Animal
/
ErbB Receptors
/
Antibodies, Monoclonal
Type of study:
Prognostic_studies
Limits:
Animals
/
Female
/
Humans
Language:
En
Journal:
Anticancer Res
Year:
2009
Document type:
Article
Affiliation country:
Estados Unidos