Overall, our work reveals that PDX modeling of CRC can be predictive of clinical survival outcomes; that integration of PDX modeling with in vivo selection can give rise to highly metastatic PDX derivatives which can be profiled transcriptomically and metabolically to identify key drivers of metastatic progression; and that PCK1 and DHODH represent key metabolic drivers of CRC metastasis and therapeutic targets in CRC. Here, DHODH is linked to colorectal carcinoma.