IRS1 and malignant mesothelioma: Alterations in IRS expression have been documented for certain neoplastic diseases, such as malignant mesothelioma, and hepatocellular, pancreatic and breast cancer.39, 72, 73, 74, 75 Although the mechanism by which IRS-1 supports tumor growth is not fully understood, a plausible hypothesis is that IRS-1 amplifies the signal of the IGF-1R.