Abstract

Central nervous system (CNS) atypical teratoid/rhabdoid tumors (AT/RT) are among the pediatric malignant tumors with the worst prognosis. Insulin-like growth factor I receptor (IGF-IR) protects cancer cells from apoptosis induced by a variety of anticancer drugs and radiation. IGF-IR is expressed in primary CNS AT/RT as detected by immunohistochemistry. Moreover, there is evidence for the potential presence of an autocrine/paracrine IGF-I/II/IGF-IR loop in CNS AT/RT. IGF-IR antisense oligonucleotide treatment of human CNS AT/RT cells results in significant down-regulation of IGF-IR mRNA and protein expression, induction of apoptosis, and chemosensitization to doxorubicin and cisplatin. These studies provide evidence for the influence of IGF-IR on cellular responses to chemotherapy and raise the possibility that curability of selected CNS AT/RT may be improved by pharmaceutical strategies directed toward the IGF-IR