Project Portugal 2030

Summary

The main goal of SweetChild is to unveil the glycan code and associated molecular pathways of paediatric sarcomas (PS), identifying novel stratifying biomarkers of disease, PS glycosignatures, and ultimately paving the way for the design of novel and effective therapeutic strategies. The role of altered glycan expression in cancer development and progression has been well described by us and others. Indeed, the abnormal expression of specific cancer-associated glycans plays crucial roles along the carcinogenesis pathway. However, there has been insufficient studies exploring the role of altered glycosylation in sarcomagenesis, particularly in pediatric setting. Primarily, this is attributed to the rarity of the disease, the limited availability of clinical samples, the lack of reliable in vitro and in vivo models and modest research funding. These factors have been hampering the development of innovative approaches and significant advancements in PS research. Acknowledging the obstacles in studying a rare disease where sample availability is scarce, we are herein proposing a novel approach where we will identify PS aberrant glycan patterns and decipher associated molecular signatures based on a bivalent strategy: i) in vitro characterization and functional validation of glycans playing a key role in PS development and aggressiveness using unique/advanced glycoengineered cell models of disease, and ii) in situ clinical multi-omic characterization and validation of glycans candidates and associated molecular pathways resorting to a valuable PS tissue clinical cohort. Unfortunately, in the last 40 years the prognosis and survival rates of PS patients hardly changed, and this is mainly due to the lack of significant advancements in research in this field. Thus, we truly believe that SweetChild focus on an important clinical gap in the oncology field, by contributing with novel knowledge that will improve future clinical diagnosis and treatment of PS patients. Additionally, by implementing our findings in the clinical practice, we will be contributing to informed clinical decisions as well. Taking advantage of our internationally recognized expertise in glycobiology in cancer, allied to the devoted support of CHUSJ expert clinicians, medical doctors and pathologists, SweetChild will leap forward PS biomedical research. By working beyond the established state of the art, currently mainly based on genetic alterations (translocations, amplifications and mutations), and by using our two complementary approaches, such the powerful multiomic approach on PS tissues samples, we will propel forward PS research in an innovative way. In conclusion, SweetChild represents my commitment as a scientist to contribute to the development of high impact research that will benefit cancer patients’ outcomes, improving their quality of life and survival prognosis. Specifically, we propose an innovative scientific strategy, heavily relying on multiomic approaches, to achieve our ambitious aim of disclosing the poorly understood role of altered glycosylation features in PS.