Overview
- UC San Diego researchers report in Blood on Oct. 20, 2025 that pairing bortezomib with the autophagy inhibitor Lys05 reduced disease burden and extended survival in mouse models.
- Experiments showed that bortezomib triggers HSF1 activation in AML cells, which increases lysosome-mediated autophagy to compensate for blocked proteasomes.
- Genetic inactivation of HSF1 made AML cells responsive to bortezomib in human cell studies and in mice.
- The drug combination demonstrated activity across diverse AML cell lines and patient samples irrespective of specific genetic mutations.
- The team is seeking additional agents to disable backup survival pathways with the aim of advancing effective combinations into clinical trials.