Anti-ERBb4 targeted therapy combined with radiation therapy in prostate cancer. Results of in vitro and in vivo studies.
OBJECTIVE
To evaluate the efficiency of anti ErbB4 targeted therapy combined with irradiation (XRT) over each modality alone in prostate cancer.


RESULTS
Clones with high ErbB4 expression grew faster than those with low ErbB4 expression. XRT inhibited the growth of both expressive and non-expressive ErbB4 cells, while mAb inhibited only high ErbB4-expressing cells. The combination of XRT and mAb resulted in a 30% reduction of the survival of high ErbB4 expressing cells over XRT alone (p = 0.013). In tumor bearing mice the tumor size in the combined arm was 1 mm at 4 weeks compared to 2-3 mm and 4-5 mm in the radiation and mAb arms (p' value of 0.02 and 0.087 respectively).


METHODS
Clones with low and high expression of ErbB4 isolated by a limited dilution technique from an androgen-independent Cl-1 cell line were used. The cells from these clones were exposed to XRT (single dose of 2-6 Gy) and to anti-ErbB4 monoclonal antibody (mAb). The XTT test was used to measure cell survival. In addition, tumor-bearing nude mice were treated either by XRT, mAb or by a combined treatment. Tumor sizes were recorded at given time points.


CONCLUSIONS
Anti ErbB4 combined with XRT is possibly more effective than each modality alone in prostate cancer.
Vexler
Akiva
A
Oncology Division, Tel-Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
Lidawi
Ghalib
G
Loew
Vered
V
Barnea
Itay
I
Karaush
Victoriya
V
Lev-Ari
Shahar
S
Shtabsky
Alexander
A
Ben-Yosef
Rami
R
D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D003131:Combined Modality Therapy; D004354:Drug Screening Assays, Antitumor; D066246:ErbB Receptors / Q000737:chemistry* / Q000276:immunology; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D008297:Male; D051379:Mice; D008819:Mice, Nude; D011471:Prostatic Neoplasms / Q000276:immunology* / Q000628:therapy*; D066247:Receptor, ErbB-4; D013997:Time Factors
D000911:Antibodies, Monoclonal; C587689:ERBB4 protein, human; D066246:ErbB Receptors; C587690:Erbb4 protein, mouse; D066247:Receptor, ErbB-4