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Modelling Brain Metastases

Identifying novel therapeutics that block the metastatic process and validating the predictive ability of our brain metastases signature


Brain metastases is the most common type of cerebral tumour in adults, occurring 10 times more often than primary brain cancers.

The inherent abilities of a primary tumour cell that is capable of initiating a Brain Metastases (BM) closely resembles the abilities of a cancer stem cell (CSC). We hypothesize that a subgroup of CSCs, termed Brain Metastasis-Initiating Cells (BMICs), are responsible for the initiation of BM and are identifiable by an exclusive subset of genes that regulate self-renewal and metastasis.

Despite the prevalence and lethality of BM, there is no clinically relevant model that fully reflects metastasis in patients. We have generated a novel human patient-derived xenotransplantation model of BM that allows for interrogation of each phase of the metastatic process from lung to brain. From this, we are identifying novel BMIC regulators and characterizing a unique BM signature.

Through our collaborations we are validating our findings in silico, in primary lung cancer patient samples, and in screening novel BM therapeutics. We will also explore the validity of these findings in BM from breast and melanoma carcinomas.

Collaborators

Picture Name Organization
Charles Swanton, FRCP, PhD Picture Charles Swanton, FRCP, PhD Clinician Scientist, The Francis Crick Institute; Professor, Cancer Medicine, University College London Hospitals and Cancer Institute
Andrew Craig, PhD Picture Andrew Craig, PhD Associate Professor, Cancer Research Institute, Queen's University
Jason Moffat, PhD Picture Jason Moffat, PhD Associate Professor, Donnelly Centre for Cellular and Biomolecular Research, University of Toronto
Sean Morrison, PhD Picture Sean Morrison, PhD Director, Children's Medical Center Research Institute at UT Southwestern (http://cri.utsw.edu/); Investigator, Howard Hughes Medical Institute

Funders

Impacts

Sheila Singh

Sheila Singh

Principal Investigator