Rationale for dual treatment targeting the IGF-1R signaling pathway in RMS. Rapamycin inhibits mTOR signaling, preventing inhibitory feedback on IRS-1 which allows proliferative signals from IGF-1R to IRS-1, PI3K, and AKT. Dual treatment using rapamycin in combination with IGF-1R inhibition, such as monoclonal blocking antibodies, prevents signaling to these critical progrowth signaling nodes.