We think that discrepancies between increased Igf1 expression and resistance to devolvement of LLC in IGF1R-deficient mice could also be due to differential transcriptional regulation of Igf1. Specifically, in pancreatic and breast cancer models, macrophages and fibroblasts were shown to be the main producers of IGF1, supporting drug resistance and metastasis of cancer cells [39, 40]. This evidence concerns the gene IGF1 and breast cancer.