The high expression of IR-A in many cancer types and its ability to initiate mitogenic signaling in response to IGF-II, as well as the presence of signaling-competent hybrid receptors may have been a major factor in the outcome of clinical trials for IGF-IR targeting antibodies and other inhibitors and has emerged as a major consideration in the design of IGF-axis targeting drugs. The gene discussed is IGF1R; the disease is cancer.