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As the efficacy of single-agent metabolic inhibitors is often limited by metabolic plasticity, developing rational combination therapies based on the coordinated targeting of oncogenic signaling and its downstream metabolic dependencies holds promise for systematically overcoming resistance and achieving more durable therapeutic benefits in tumors with specific genetic backgrounds

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To examine whether transsulfuration may be substrate-limited, we examined whether excess cystathionine or homocysteine could rescue viability under cystine starvation in a panel of NSCLC cell lines (Figure S1A)

The first sample was dissolved in methanol with 0.1 mL of 50 % of the SSA and the second sample in an ammonium buffer pH 3.5 [H 2 O/ACN (90:10) (v/v) + 1 mM NH 4 (CH 3 COO)] with CH 3 COOH