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Epidermal growth factor receptor blockade by antibody IMC‐C225 inhibits growth of a human pancreatic carcinoma xenograft in nude mice
Author(s) -
Overholser Jay P.,
Prewett Marie C.,
Hooper Andrea T.,
Waksal Harlan W.,
Hicklin Daniel J.
Publication year - 2000
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/1097-0142(20000701)89:1<74::aid-cncr11>3.0.co;2-k
Subject(s) - epidermal growth factor , epidermal growth factor receptor , cancer research , pancreatic tumor , medicine , pancreatic cancer , pancreas , receptor , endocrinology , pancreatic disease , growth factor receptor , cetuximab , blockade , cancer , colorectal cancer
Abstract BACKGROUND Pancreatic carcinoma is associated with a poor prognosis, and treatment options for patients with this disease are limited. The epidermal growth factor (EGF) receptor and its ligands are overexpressed in human pancreatic carcinoma and may contribute to the pathophysiology of these tumors. METHODS The anti‐EGF receptor monoclonal antibody IMC‐C225 was used to determine the effects of EGF receptor blockade on the growth of human pancreatic carcinoma BxPC‐3 cells in vitro. Athymic mice bearing established (200 mm 3 ) subcutaneous BxPC‐3 xenografts were treated with IMC‐C225 (17 or 33 mg/kg every 3 days) alone or in combination with 5‐fluorouracil (17 mg/kg twice weekly). RESULTS IMC‐C225 inhibited exogenous ligand‐stimulated tyrosine phosphorylation of the EGF receptor on BxPC‐3 tumor cells. Treatment of BxPC‐3 cells with IMC‐C225 inhibited DNA synthesis (23.8%) and colony formation in soft agar (45.6%). IMC‐C225 treatment significantly suppressed the growth of BxPC‐3 tumors compared with treatment with vehicle alone ( P = 0.003). Combination therapy with IMC‐C225 and the chemotherapeutic agent 5‐fluorouracil enhanced the antitumor effects compared with either agent alone and resulted in regression of pancreatic tumors in several animals. Histologic examination of pancreatic tumors from mice treated with IMC‐C225 showed extensive tumor necrosis that coincided with a substantial decrease in tumor cell proliferation and an increase in tumor cell apoptosis. CONCLUSIONS These data suggest that IMC‐C225 affects the growth of pancreatic tumors by inhibiting EGF receptor–dependent proliferation and survival, and demonstrates the potential for therapeutic application of IMC‐C225 antibody in the treatment of human pancreatic carcinoma. Cancer 2000;89:74–82. © 2000 American Cancer Society.