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Additional information Peer review information Nature Communications thanks Keith Blackwell and the other, anonymous, reviewer(s) for their contribution to the peer review of this work

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The Phase 1 trial NCT00742911, the foundational trial, established the safety and tolerability of this combination in patients with liver metastases but observed no objective responses, highlighting the central challenge of translating this strategy into potent clinical efficacy

Practical injection tips Several practices improve injection experience and consistency: Allow refrigerated solution to warm slightly before injection to reduce discomfort Clean injection sites with alcohol and allow to dry completely Inject slowly rather than rapidly pushing the plunger Keep a log of injection sites to ensure proper rotation If using acetic acid reconstitution, dilute with BAC water immediately before injection Because IGF-1 can lower blood sugar, having a small carbohydrate source available after injection helps prevent hypoglycemic symptoms

& Giannaccini, G