Therapeutic Assessment of Targeting ASNS Combined with l-Asparaginase Treatment in Solid Tumors and Investigation of Resistance Mechanisms.

ABSTRACT: Asparagine deprivation by l-asparaginase (L-ASNase) is an effective therapeutic strategy in acute lymphoblastic leukemia, with resistance occurring due to upregulation of ASNS, the only human enzyme synthetizing asparagine (Annu. Rev. Biochem. 2006, 75 (1), 629-654). l-Asparaginase efficacy in solid tumors is limited by dose-related toxicities (OncoTargets and Therapy 2017, pp 1413-1422). Large-scale loss of function genetic in vitro screens identified ASNS as a cancer dependency in several solid malignancies (Cell 2017, 170 (3), 564-576.e16. Cell 2017, 170 (3), 577-592.e10). Here we evaluate the therapeutic potential of targeting ASNS in melanoma cells. While we confirm in vitro dependency on ASNS silencin

SUBMITTER: Apfel V 

PROVIDER: S-EPMC7887857 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature