title: Blockage of insulin-like growth factor-I receptor inhibits the growth of Ewing's sarcoma in athymic mice.
abstract: 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.
authors.affiliation: Laboratorio di Ricerca Oncologica, Istituti Ortopedici Rizzoli, Bologna, Italy.
authors.forename: K
authors.initials: K
authors.lastname: Scotlandi
authors.forename: S
authors.initials: S
authors.lastname: Benini
authors.forename: P
authors.initials: P
authors.lastname: Nanni
authors.forename: P L
authors.initials: PL
authors.lastname: Lollini
authors.forename: G
authors.initials: G
authors.lastname: Nicoletti
authors.forename: L
authors.initials: L
authors.lastname: Landuzzi
authors.forename: M
authors.initials: M
authors.lastname: Serra
authors.forename: M C
authors.initials: MC
authors.lastname: Manara
authors.forename: P
authors.initials: P
authors.lastname: Picci
authors.forename: N
authors.initials: N
authors.lastname: Baldini
mesh_terms: 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
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D017451:Receptors, Somatomedin; D013498:Suramin