For FLO-1 LM cell line xenografts, 5 x 10⁶ cells suspended in 100 ul of 1:1 PBS and Matrigel (BD Biosciences) were subcutaneously injected into the right flank of ~6 week-old female nonobese diabeticsevere combined immunodeficient interleukin-2RKO (NSG) mice. PDXs were established and implanted into a dorsal intramuscular pocket of NSG mice as previously described. Mice were randomized to SG deplete or control chow ad libitum (AIN93G rodent diet, Specialty Feeds, Australia) and dosed with eprenetapopt (100 mg/kg) or 0.9% saline, intraperitoneally injected daily, once tumors reached 100 mm³. Tumor volume was assessed blinded to treatment group with caliper measurements every 3 to 4 days and calculated using the formula (length x weight2)/2. Metastatic spread was determined by bioluminescence imaging as previously described involving weekly monitoring using the Xenogen IVIS 100 Imaging System (Caliper Life Science). At experimental end point (tumor volume > 1400 mm³), the whole mouse and its organs were imaged to determine the extent and distribution of metastases. Tumors were weighed and tumor growth inhibition was calculated with the formula [1 - (Tf- Ti)/mean(Cf - Ci)] x 100, where Tf, Ti, Cf, and Ci represent final (f) and initial (i) tumor volume of drug treated (T) and control (C) animals, respectively.

Xenograft tumors were generated by randomly injecting 1 x 10⁶ MOLM14 shCTRL or shSLC7A11 cells into the tail veins of NOD/SCID IL-2 receptor g-chain-null mice (NSG) aged 6-9 weeks. Fourteen days after injection, doxycycline (200 mg/mL) and sucrose (1% weight:volume) were added to the drinking water of these animals. After 3 days, the mice were randomly treated with a daily intraperitoneal injection of APR-246 (100 mg/kg) or vehicle (phosphate-buffered saline [PBS]) for 4 days.