ASNS and neoplasm: Most solid tumors can activate the expression of asparagine synthetase (ASNS) through a stress response effector activating transcription factor 4 (ATF4) and employ de novo biosynthesis as an alternative source of Asn, which maintains the intracellular Asn levels to support tumor cell proliferation in the absence of exogenous Asn and thereby abrogate the effectiveness of ASNase treatment30–32.