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Research

META-DORM

Principal investigator: Martin KNIGHT
Co-investigator(s): Stefaan VERBRUGGEN
Funding source(s): Commission of the European Community
 Start: 01-01-2018  /  End: 31-07-2020
 Amount: £137844
SEMS division:

While cancer survival rates have improved significantly in recent years, survival decreases dramatically after tumour metastasis. One of the most common sites for metastatic tumours from breast and prostate cancers to develop is bone. Intriguingly, evidence suggests that, once they have invaded the bone marrow, individual metastatic cancer cells can persist for years in a quiescent or “dormant” state, and are resistant to both radiation and chemotherapy treatment. These dormant cells can reside for months or years while the cancer is in remission, and then “reactivate” without warning to form new, usually fatal, skeletal lesions. Tumour cells achieve this by “hijacking” the normal bone remodelling cycle, a homeostatic balance between bone formation and resorption, to form a metastatic niche within the marrow.

However, the signalling mechanisms that cause metastasis and dormancy, particularly in such a mechanically active environment, are poorly understood. The project will focus on a specific cellular mechanosensor, the primary cilium, which has been implicated in the development of cancer and is known to be involved in bone formation.

Therefore, the goal of this project is to investigate the biochemical and physical interactions between bone and cancer cells, both during dormancy and mechanical stimulation, to provide new insight into bone metastatic lesions and explore novel therapeutic targets to prevent cancer metastasis.

Dr. Stefaan Verbruggen was awarded a Marie Skodowska-Curie Global Research Fellowship to work with Prof. Martin Knight in the field of cancer mechanobiology and primary cilia. Stefaan will spend the first year of the fellowship in Prof. Chris Jacobs’ lab at Columbia University, to learn more about how cancer metastasises and spreads to bone. before returning to Prof. Martin Knight’s lab at Queen Mary University of London for the final year.