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April 19, 2026Cancer Research

Abstract LB354: Pharmacologic TSC2 inhibition sensitizes acute myeloid leukemia to proteasome inhibition via mTORC1 mediated mitochondrial catastrophe

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Authors

SPShakti PattanayakBTBoaz TiroshOHOmid Hajihassani

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Overview

Pharmacologic TSC2 inhibition enhances cytotoxicity in acute myeloid leukemia, suggesting new treatment strategies.

Key Points

  • This study aims to explore TSC2 inhibition as a therapeutic strategy to sensitize acute myeloid leukemia to proteasome inhibitors.
  • Developed AcTor, a small-molecule TSC2 inhibitor, through medicinal chemistry and in silico screening.
  • Evaluated AcTor combined with the proteasome inhibitor ixazomib in AML cell lines and patient-derived samples.
  • Conducted transcriptomic profiling to analyze stress responses in treated cells.
  • AcTor significantly increased the effectiveness of ixazomib across diverse AML models.
  • Combination treatment triggered rapid apoptosis via mitochondrial dysfunction.
  • In vivo studies showed decreased leukemic burden and effective elimination of circulating blasts and leukemic stem cells.

Cite This Study

Pattanayak et al. (2026) studied this question.

synapsesocial.com/papers/69e471c5010ef96374d8dfb5https://doi.org/10.1158/1538-7445.am2026-lb354
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