Integrated Glycomics for Cancer Precision Medicine

Breast Cancer is the most commonly diagnosed cancer in Europe and remains the first cause of cancer death in women (nearly 92,000 deaths in 2020). Precision medicine uses data-driven insights to reflect the heterogeneity of patients and improve cancer care by offering actionable oncology treatment options. Tumour tissue heterogeneity is the leading cause for inter-patient variation in treatment response. One of the largest sources of tissue heterogeneity arises from post-translational glycosylation of proteins and aberrant glycosylation is a hallmark of breast and other cancers. Yet, substantial gaps remain in our knowledge of cancer glycans. Glycomics (the comprehensive study of the glycome) offers the potential to provide the global glycosylation status (GlycoMap) of a patient and shed new light on tumour heterogeneity to guide precision medicine. This project aims to address the substantial knowledge gap in breast cancer tumour glycosylation data by developing an integrated glycomics workflow to produce patient-specific 'GlycoMaps'. By including glycosaminoglycan (GAG) 'omics from intact GAGs for the first time, combined with other glycan analyses will enable the generation of Breast Cancer GlycoMaps from resistant and drug-sensitive patient-derived organoids (mini avatars of tumour tissue), defining residual tumour tissue following treatment that causes relapse and metastasis. The mission and design of the GlycoMap project is to train the researcher, who has a background in GAGomics, proteoglycan biology and bioinformatics, with expanded skills and expertise in N-/O-glycomics, organoid culture, hi-resolution 3D imaging and advanced bioinformatics in the context of breast cancer, augmenting her future career opportunities, as well as establishing unbiased top-down integrated glycomics to support breast cancer analyses, diagnostics and the development of novel treatments.