Here we report that pharmacological or genomic blockade of IGF-1R induces a protective reprogramming of cancer cells to stimulate signal transducer and activator of transcription 3 (STAT3)-dependent transcriptional increases in IGF-2 in cancer cells, promoting tumour–stromal communication through IGF-2R-dependent paracrine signalling. The gene discussed is IGF2; the disease is neoplasm.