Blockage of insulin-like growth factor-I receptor inhibits the growth of Ewing's sarcoma in athymic mice.
Innovative, more effective treatment modalities are needed for Ewing's sarcoma (ES), a neoplasm with a disappointingly low survival rate despite the use of aggressive multimodal therapeutic approaches. We have previously shown (K. Scotlandi et al, Cancer Res., 56: 4570-4574, 1996) the existence and the pathogenetic relevance of an autocrine loop that is mediated by the insulin-like growth factor-I receptor (IGF-IR) and is crucial for the survival and proliferation of ES cells in vitro. In this study, we report that the IGF-IR-blocking monoclonal antibody alphaIR3 may also significantly inhibit ES cell growth in vivo. In particular, in almost one-half of the animals tested, after s.c. inoculation with TC-71 ES cells, the blockage of IGF-IR by alphaIR3 induced a complete regression of tumors that developed, which suggests that IGF-IR is valuable as a specific target for novel therapeutic strategies. In addition, suramin, a drug that can interfere with growth factor binding with their receptors, inhibited the tumorigenic and the metastatic ability of TC-71 cells and, therefore, is a promising agent to be combined with conventional cytotoxic drugs for the design of more effective therapeutic regimens.
Scotlandi
K
K
Laboratorio di Ricerca Oncologica, Istituti Ortopedici Rizzoli, Bologna, Italy.
Benini
S
S
Nanni
P
P
Lollini
P L
PL
Nicoletti
G
G
Landuzzi
L
L
Serra
M
M
Manara
M C
MC
Picci
P
P
Baldini
N
N
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000473:pathology / Q000517:prevention & control*; D005260:Female; D051379:Mice; D008819:Mice, Nude; D017451:Receptors, Somatomedin / Q000037:antagonists & inhibitors*; D012512:Sarcoma, Ewing / Q000473:pathology / Q000517:prevention & control* / Q000556:secondary; D013498:Suramin / Q000627:therapeutic use*; D014183:Transplantation, Heterologous
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D017451:Receptors, Somatomedin; D013498:Suramin