Although initial studies with antibodies targeting insulin-like growth factor receptor (IGF-IR) showed promising potential for the treatment of patients with bone and soft tissue sarcomas, phase II clinical trials revealed variable results, which implied activation of alternative signaling pathways leading to therapy resistance.
Akt activation by the IGF-1 receptor (IGF-1R) has been posited to be a mechanism of intrinsic resistance to mTORC1 inhibitors (rapalogues) for sarcomas.
Clinical trials for patients with sarcoma have demonstrated impressive anti-tumor activity in cases where the IGF-1 pathway is activated, such as in Ewing sarcoma; however, acquired resistance has been common.
Inhibitors of the tyrosine kinase receptors, such as IGF-1R, c-kit, PDGFR, VEGFR, or the mTOR signaling pathway, proteasome, angiogenesis, and stress response proteins are under clinical evaluation against sarcomas.
We investigated the molecular weights of IGF-II forms and their ability to form complexes with IGF binding proteins (IGFBPs) in conditioned culture media (CM) from 12 paediatric soft tissue sarcoma (STS) cell lines and from two healthy fibroblast lines.
Epidermal growth factor (EGF) and insulin-like growth factor-I (IGF-I) receptors are implicated in the development and progression of several malignancies including osteogenic and soft tissue sarcomas (STS).