Sugarcoating a bitter pill: Identifying how mucinous tumours use glycobiology for chemoresistance

Project Outline

Mucinous colorectal cancers are easily identifiable early in a patient’s care due to their extracellular glycan (sugar)-dominated mucus, which accounts for more than 50% of tumour volume. This early identification and the unique changes in the biology that separate mucinous from non-mucinous disease should empower precision medicine. However, no specific treatments exist for mucinous colorectal cancers. Instead, patients follow the same pathway as those with non-mucinous colorectal cancers. Unfortunately, on these parallel care pathways patients with mucinous disease have a significantly worse survival than those with non-mucinous colorectal cancer, in part due to a poorer response to chemotherapy.

Laboratory evidence has shown that cells from mucinous tumours are not innately resistant to chemotherapeutic agents, but rather that the glycan-rich mucus they secrete provides them with a chemoprotective microenvironment. We therefore need to develop specific therapies to target the innate biology of mucinous colorectal cancers to refine or replace the current treatments. To do this we first need to understand the chemoprotective microenvironment generated by mucinous tumours, then find ways to alter this for patient benefit. This project will make this step to improve clinical outcomes. 

The student will join an interdisciplinary team using the unique opportunities available within the Manchester cancer research ecosystem to advance our knowledge of mucinous colorectal cancer. A partnership between academic research labs at The University of Manchester and surgical consultants at The Christie Hospital will isolate mucus from patient tumours and build on our existing living biobank of mucinous colorectal cancer. The student will leverage these resources to catalogue what chemoprotective mucus is made from, how these biomolecules interact with chemotherapy agents and identify targetable pathways required for mucus production. The student will gain extensive skills in molecular and cellular biology and importantly, an understanding of the glycobiology in colorectal cancer. 

Applications for this project are now open. Please complete your application on The University of Manchester website.