Study identifies a new driver and therapeutic vulnerability of bone metastasis
MD Anderson Research Highlight May 21, 2025
One of the most common sites for cancer to metastasize is the bone. Unfortunately, patients with bone metastases have a poor prognosis and most treatments are focused on palliative care, highlighting a need for better therapeutic strategies. Because metastatic cells are known to reprogram metabolic states to adapt to their new environments, Li Ma, Ph.D., and colleagues examined the role of lipid metabolism – the breakdown and creation of fats – in lab models of bone metastasis. Using in vivo CRISPR activation screening, they identified acyl-CoA binding protein (ACBP) as a driver of bone metastasis due to its vital role in regulating lipid metabolism. ACBP stimulates fatty acid oxidation (FAO) while protecting against lipid peroxidation and ferroptosis – a form of iron-dependent programmed cell death. In models of cancer cells that are highly bone-metastatic, knocking out ACBP completely stopped bone metastasis, suggesting its potential as a therapeutic target. The researchers also found two therapeutic strategies – blockade of FAO or treatment with a ferroptosis inducer – that inhibit bone metastasis, meriting further investigation. Learn more in Science Translational Medicine.
Bone metastasis remains a major clinical challenge. By identifying ACBP as a metabolic driver of this process and demonstrating the efficacy of targeting lipid metabolism in preclinical models, our work opens new therapeutic avenues for halting bone metastasis.