GLYCOANALYTICS · Glycoanalytics-guided discovery of novel biomarkers and therapeutic glycoenzyme inhibitors for cancer

Gastric (GC) and colorectal cancer (CRC) are major contributors to cancer-related deaths worldwide and current therapies lack efficacy. Thus, it is crucial to search for novel therapeutics to combat the increasing toll these cancers place on society globally. Glycosylation is the process by which complex carbohydrates (or glycans) are attached to lipids and proteins and is orchestrated by a suite of glycosyltransferases and glycosidases, collectively known as glycoenzymes. Glycosylation mediates a plethora of cellular processes such as cell-cell communication and cell adhesion andaberrant protein glycosylation is involved in cancer progression by influencing cell signalling, metastasis and immune evasion. Thus, glycosylation offers a largely overlooked class of biomolecules that hold promise as therapeutic targets. Taken together, this project aims to implement glycoanalytical approaches for the development of novel therapeutic strategies for GC and CRC treatment and reveal new insights into the roles of glycosylation in cancer biology. State-of-the-art analytical approaches based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) will be applied to develop comprehensive knowledge of the glycome and glycoproteome of GC and CRC cell lines, tissues and patient-derived organoids. The outputs from these comprehensive glycoprofiling exercises will reveal the key glycoenzymes to target with inhibitors and their therapeutic potential and mechanisms of action. Glycan biomarkers and glycoenzyme inhibitors will also be used in combination with currently approved therapeutic drugs for cancer such as monoclonal antibodies (e.g. Cetuximab) to evaluate combinatorial effects. Overall, this project will provide the most detailed and clinically relevant glycoprofiles for GC and CRC and will pioneer the application of these biomarkers in the GC and CRC therapeutic settings to reduce the global burden of these deadly cancers.