Discovering the secrets of cancer dormancy in bone

Cancers in bone are incurable. Bone lining cells cause a small proportion of cancer cells to become dormant (quiescent). Dormant cells evade treatments that target dividing cells and reactivate to cause relapse. To enable development of dormancy therapeutics we need to understand how dormant cells function and the role of the dormancy niche. I discovered a novel cancer drug that kills 50% of dormant myeloma cells in mice, delaying relapse and improving survival. This is the first drug to kill dormant cells, yet mice still relapse, indicating we need to kill all dormant cells to cure the disease. To eradicate dormant cells, we need to understand their weaknesses. I developed models of myeloma dormancy and single-cell techniques to study the dormancy niche. This project will use single-cell transcriptomics and metabolomics to generate a holistic landscape of the dormancy niche. I will use omics data, alongside existing findings showing reactive oxygen species and oxidative damage are altered in dormant cells, to decipher weaknesses of dormant cells. We will then examine whether targeting intrinsic vulnerabilities and/or the niche can kill dormant cells, without harming healthy cells. This will be a step change towards future therapeutics that eliminate dormant cancer cells in bone.