Several factors have been proposed as contributing to this lack of efficacy, namely: (i) compensatory growth signaling by insulin receptor (IR) isoform A that binds IGF-2 with high affinity and is highly expressed on some cancer cells; (ii) signaling by hybrid receptor IR:IGF-1R that can bind insulin and IGF; (iii) compensatory signaling and ERK activation by other receptor tyrosine kinases (RTKs); (iv) the potential role of nuclear IGF-1R in promoting tumor cell proliferation9; and (v) the lack of biomarkers that could aid in identifying a responsive patient population. This evidence concerns the gene INSR and neoplasm.