What do all cancers have in common?
When talking about cancer, there's an intriguing question: What do all cancers have in common? One answer might surprise many: aberrant O-glycosylation.
What is O-glycosylation?
At its core, O-glycosylation is the attachment of sugars to proteins, specifically to their oxygen atom. Think of these sugars as "tags" that regulate various cellular functions such as communication between cells, protein stability, and cellular signaling. In the world of cancer, these "tags" can get mixed up, leading to aberrant or irregular O-glycosylation.
How does cancer lead to aberrant O-glycosylation?
· Initiation Steps: Our body starts O-glycosylation by adding a sugar known as GalNAc to proteins. In cancer, this process might start in a disordered way due to enzyme dysregulation.
· Enzyme Expression: Post the initiation, enzymes (glycosyltransferases) work to add more sugars to the chain. Cancer can cause these enzymes to overwork, underwork, or behave oddly, leading to unusual sugar tags.
· Enzyme Dysregulation: There are also enzymes that remove specific sugars. When these become erratic, we can see more unusual sugar tags.
· Cellular Infrastructure Disruptions: Two major cellular structures, the Golgi and ER, oversee the glycosylation process. Rapidly growing tumor cells can mess up these structures, influencing how sugars are tagged onto proteins.
· Resource Limitations: To tag proteins, we need sugar donors. If there's a change in the availability of these sugars, glycosylation might not complete properly.
· Tumor Environment: Factors like oxygen levels, pH changes, and nutrients can push the cellular machinery to make atypical sugar tags.
The Tn and STn Antigens.
Two significant sugar tags (or antigens) that stand out in the context of cancer are Tn and STn. In regular, healthy tissues, Tn is almost never seen, and STn only occasionally. However, in cancerous tissues, their presence is notably amplified. These changes offer potential landmarks for cancer diagnostics and treatments.
The Challenges in Targeting Tn and STn in context of the target protein
Despite the potential of these sugar tags, generating antibodies specifically targeting Tn and STn and its protein carrier has been a challenge due to the insufficient immune response in current animal systems.
The Future: Combotope Therapeutics Discovery Platform
Our phage discovery platform overcome previous limitations, producing antibodies in animal-free systems that can target these sugars and their protein carrier effectively, introducing a new frontier in cancer therapeutics.