ideasIdea
A bone marrow niche on a chip to study human dormancy
Dormant cancer cells hide in bone marrow. A lab-built model of that hiding place would let us watch them sleep and wake, and test drugs on them.
Microfluidic and organ-on-chip systems can now sustain human haematopoietic niches with mesenchymal stroma, osteoblasts and vasculature under flow. Adding patient-derived tumour cells creates a human dormancy model with live-cell imaging, in which awakening triggers such as inflammation, chemotherapy or niche disruption can be dialled in and quantified.
Hypothesis
Human marrow-niche chips reproduce the entry into and exit from dormancy and rank pro-dormancy or dormancy-killing compounds concordantly with in vivo models, making them a valid first-line assay.
Rationale
Dormancy depends on niche cell contacts and flow that plastic dishes cannot supply, which is why the field is stuck on mouse studies. Liver and gut chips have already been accepted for some regulatory-grade toxicology, so the engineering path is known.
What would test it
Benchmark a chip against paired in vivo data with a blinded compound set of known dormancy modulators and inactive controls; publish concordance, cost and throughput.
Maturity
preclinical evidence
Who has to act
engineering
Cost to try
Medium ($1M to $50M)
Years to first evidence
6
Bottlenecks it attacks
- Dormant cells and minimal residual disease · After a 'successful' treatment, cells can sleep for years then relapse. We can barely detect them and cannot target them.
- Preclinical models that do not predict people · Nine in ten cancer drugs that work in mice fail in humans. Our models are the reason.