OSI-906 overcomes bortezomib resistance in vivo. Animal studies were performed in C.B-17 severe combined immunodeficiency male mice with flank xenografts of 8226.BR cells. Drugs were administered via intraperitoneal (i.p.) injections on days 1 and 4 of each week. Tumors were measured on each day of treatment by a researcher who was blinded to the treatment assignments, and volumes were calculated using the equation 1/2 (length × width²). (A) Pilot dose escalation studies were performed with OSI-906, in which mice received drug weekly on days 1 and 4 (n = 5). (B) Combination regimens of OSI-906 and bortezomib were tested in cohorts of tumor-bearing animals randomized to either vehicle, OSI-906 alone, 15 mg/kg OSI-906 + 0.5 mg/kg bortezomib, 20 mg/kg OSI-906 + 0.5 mg/kg bortezomib, or 0.5 mg/kg bortezomib (n = 6).