A Novel ACLY Inhibitor Induces Transcriptional and Metabolic Reprogramming to Overcome Tyrosine kinase inhibitor Resistance in Lymphoma. (PubMed, bioRxiv) - Oct 11, 2026 - "In ALK inhibitor-sensitive SUPM2, VCB1 showed an IC₅₀ of 0.299 μM and retained potency in lorlatinib-resistant SUPM2-LR1000 cells (1.62 μM), whereas BMS-303141 was substantially less active (17.46 and 22.07 μM)...ACLY represents an integrated metabolic and signaling vulnerability in lymphoma. VCB1 suppresses lymphoma growth across TKI-sensitive and resistant models by disrupting lipid and nucleotide metabolism, metabolic adaptation and ISR and redox homeostasis supporting ACLY inhibition as a therapeutic strategy for TKI-resistant lymphoma."
IO biomarker • Journal • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Oncology • T Cell Non-Hodgkin Lymphoma • ACACA • ATF4 • CHAC1 • DDIT3 • DDIT4 • FASN • GCLM • PD-1 • PPARGC1A • PPARGC1B • PPP1R15A • SESN2 • TIGIT • UCK2
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Aaron R Goldman; Cosimo Lobello; David Rushmore; Hossein Borghaei; Johnvesly Basappa; Kavindra Nath; Luca Mologni; Mariusz Wasik; Nagarajan Pattabiraman; Reza Nejati; Shengchun Wang; Wujuan Zhang
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