MTOR and neoplasm: Similarly, temsirolimus (CCI-779) suppressed downstream protein phosphorylation and reduced tumor growth in ARMS xenografts via an antiangiogenic mechanism linked to mTOR/HIF-1α/VEGF signaling [338]; however, clinical trials, such as the Phase III Children’s Oncology Group ARST1431 trial, showed that adding temsirolimus to chemotherapy did not improve event-free survival in intermediate-risk RMS patients [342], highlighting the need for novel, biology-based combination strategies.