Cell and animal research (not human) · in vitro
Tsvetkov P et al., Science, 2022
Landmark T01 #1, methods and limits (CELL AND MOUSE STUDY - NOT A HUMAN TREATMENT). The cuproptosis model rests on human cancer cell lines, two single-line CRISPR screens, cell-based biochemistry and one mouse-liver experiment, with no human intervention. Main limits: (1) copper was mostly forced in with ionophores (elesclomol, disulfiram/cupric-DDC, NSC319726) and the FDX1/lipoylation dependence disappears above ~40 nM elesclomol (fig S4L-P); (2) each CRISPR screen used a single line (OVISE whole-genome; A549 metabolism-gene); (3) mouse evidence is protein changes in Atp7b-/- liver, not a survival or treatment outcome; (4) human tumour data are FDX1-vs-lipoic-acid staining correlations; (5) the paper carries an erratum. One true internal inconsistency (tumour count 208 vs n=57) plus a free-copy-vs-publisher COI contradiction are recorded below.
Source: Copper induces cell death by targeting lipoylated TCA cycle proteins. Tsvetkov P, Coy S, Petrova B, Dreishpoon M, Verma A, Abdusamad M, Rossen J, Joesch-Cohen L, Humeidi R, Spangler RD, Eaton JK, Frenkel E, Kocak M, Corsello SM, Lutsenko S, Kanarek N, Santagata S, Golub TR. Science. 2022;375(6586):1254-1261. doi:10.1126/science.abf0529. PMID 35298263; PMC9273333 (NIH author manuscript). Published 2022-03-17. Erratum: Science 2022;376(6591):eabq4855.
Verified research card EL-LM-T01-01-b-R2