Prostate cancer is the most commonly diagnosed malignancy in men, claiming over 350,000 lives worldwide annually. More than 80% of men with advanced prostate cancer will develop painful and incurable bone metastasis. New treatments for bone metastasis are urgently needed and could significantly impact patient quality of life and survival rates (currently only 29% of men with advanced prostate cancer will still be alive after 5 years).
Why prostate cancer cells metastasise to bone and by what mechanisms are big unanswered questions. Our data suggest that glycan sugar groups (found on the cell surface of and secreted by cancer cells) provide a key part of the answer. Glycans are major building blocks of life essential in virtually every biological process. This is exploited by cancer cells and changes to glycans are important in all of the cancer hallmarks.
In exciting unpublished data, we have identified a set of glycans with key roles in driving the spread of prostate cancer to bone. Importantly, drugs targeting these glycans have already been developed for other diseases and could be repurposed to also help men with prostate cancer. These glycans are also detectable in the serum and urine of men with advanced prostate cancer and we predict this can be exploited to improve diagnosis and help guide personalised treatment.
This study will use complementary expertise at Newcastle and Sheffield Universities to examine in vivo if specific glycans enable prostate cancer cell colonisation and growth in the bone, and novel multi-omic studies to identify the mechanisms involved. We will then test if glycan targeting drugs (already developed for other diseases) can prevent/inhibit the spread of prostate cancer to bone. The student will be trained in in vitro models of cancer cell behaviour, mouse models of prostate cancer, bioluminescence imaging, 2-photon microscopy, micro-CT, transcriptomics, proteomics and glycomics approaches.
The project will also monitor a panel of glycans in patient serum and urine using pre-validated sandwich ELISA tests. We have assembled several large cohorts of patient samples for this (comprising >2000 serum/urine samples) and these will be ready to test at the start of the project. The student will use these cohorts to validate biomarker sensitivity/specificity and calculate threshold values for each glycan. We have already developed and patented a similar test to distinguish benign and aggressive prostate cancer (known as GlycoScore) and will begin commercialising our assay next year. This project will help develop a similar test to specifically diagnose bone metastasis (and we expect an industrial partner to be involved in this part of the project).
For more information or to discuss the project please contact Dr Jennifer Munkley email: [email protected]
Dr Ning Wang: https://www.sheffield.ac.uk/oncology-metabolism/staff/ningwang
Dr Jennifer Munkley: https://www.ncl.ac.uk/igm/staff/profile/jennifermunkley.html#publications
Benefits of being in the DiMeN DTP:
This project is part of the Discovery Medicine North Doctoral Training Partnership (DiMeN DTP), a diverse community of PhD students across the North of England researching the major health problems facing the world today. Our partner institutions (Universities of Leeds, Liverpool, Newcastle and Sheffield) are internationally recognised as centres of research excellence and can offer you access to state-of the-art facilities to deliver high impact research.
We are very proud of our student-centred ethos and committed to supporting you throughout your PhD. As part of the DTP, we offer bespoke training in key skills sought after in early career researchers, as well as opportunities to broaden your career horizons in a range of non-academic sectors.
Being funded by the MRC means you can access additional funding for research placements, international training opportunities or internships in science policy, science communication and beyond. See how our current DiMeN students have benefited from this funding here: http://www.dimen.org.uk/overview/student-profiles/flexible-supplement-awards
Further information on the programme can be found on our website: http://www.dimen.org.uk/