Metabolic rewiring is a hallmark of cancer, enabling cancer cells to sustain their aggressive behavior. Many tumor types exhibit specific amino acid auxotrophies. One of the most well-known examples is acute lymphoblastic leukemia (ALL), which is characterized by an asparagine auxotrophy, and is exploited clinically using asparaginases (ASNases). Upstream, the amino acid stress response (AAR) pathway acts as a control switch, halting global translation to redirect resources towards focused translation to overcome amino acid shortages. This led us to hypothesize that cancer types with amino acid auxotrophies could all be treated similarly by blocking the AAR pathway. here, we will investigate the therapeutic potential of blocking the amino acid stress response through GCN2 inhibition in patient-derived xenograft (PDX)models of leukemia and solid cancer subtypes. Additionally, we aim to identify reliable biomarkers that can predict sensitivity towards GCN2 inhibition.