Selective inhibition of HER2 inhibits AKT signal transduction and prolongs disease-free survival in a micrometastasis model of ovarian carcinoma.
Although first-line chemotherapy induces complete clinical remission in many cases of epithelial ovarian cancer, relapse usually occurs 18-28 months from diagnosis owing to micrometastases. The present study aimed to evaluate the effect of trastuzumab on disease-free and overall survival in a specially designed murine model of ovarian cancer (OVCAR-3), which mimicked the natural history of human micrometastatic disease. Trastuzumab can cure the mice if started soon after induction chemotherapy. It can modestly inhibit the proliferation through mitogen-activated protein kinase signal transduction and clearly inhibit AKT phosphorylation, which is involved in survival pathway. As OVCAR-3 cell lines show no HER2 amplification or overexpression, these results warrant further studies to assess the efficacy of trastuzumab in the early stage of relapse in cancer models other than those overexpressing HER2.
Delord
J P
JP
Groupe de Pharmacologie clinique et expérimentale des médicaments anti cancéreux (EA 3035), Institut Claudius Regaud, Toulouse, France. delord_j@icr.fnclcc.fr
Allal
C
C
Canal
M
M
Mery
E
E
Rochaix
P
P
Hennebelle
I
I
Pradines
A
A
Chatelut
E
E
Bugat
R
R
Guichard
S
S
Canal
P
P
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D018572:Disease-Free Survival; D005260:Female; D005434:Flow Cytometry; D005784:Gene Amplification; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000556:secondary; D051379:Mice; D008819:Mice, Nude; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors* / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015398:Signal Transduction; D015996:Survival Rate; D000068878:Trastuzumab; D014407:Tumor Cells, Cultured / Q000637:transplantation
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D051057:Proto-Oncogene Proteins c-akt; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab