Unveiling the Sweet Secret: How Pancreatic Cancer Evades Treatment
Pancreatic cancer, a formidable foe in the battle against cancer, has long eluded treatment due to its ability to disguise itself from the immune system. But now, researchers have uncovered a sweet secret: pancreatic tumours use a sugar coating to evade detection, allowing them to grow unchecked. This discovery has led to the development of a groundbreaking antibody therapy that could revolutionize pancreatic cancer treatment.
Scientists at Northwestern Medicine have made a groundbreaking discovery: pancreatic tumours cloak themselves in a sugar-based disguise, preventing the immune system from recognizing and attacking them. This sugar-coating mechanism is a key reason why pancreatic cancer is so resistant to treatment. The study, published in the AACR Journal, details the development of an innovative antibody therapy that blocks this sugar-mediated 'don't-attack' signal, offering a glimmer of hope for future cancer treatments.
For the first time, researchers identified the precise mechanism behind this sugar trick and demonstrated in preclinical mouse models that blocking it with a monoclonal antibody reawakens immune cells to target cancer cells. This breakthrough discovery has taken years of research and testing, led by Associate Professor Mohamed Abdel-Mohsen and his team.
"Inside pancreatic tumours, the immune system response is unusually suppressed. We set out to learn why and whether we could flip that environment, so immune cells attack tumour cells instead of ignoring or even helping them," Abdel-Mohsen explained. The team discovered that pancreatic tumours hijack a natural safety system used by healthy cells, displaying a sugar called sialic acid to signal to the immune system not to harm them. However, tumours exploit this system by coating a surface protein with the same sugar, allowing it to bind to a sensor on immune cells, sending a false 'stand down' signal.
"In short, the tumour sugar-coats itself, a classic wolf-in-sheep's-clothing move, to escape immune surveillance," Abdel-Mohsen added. To combat this, the team developed monoclonal antibodies to block the sugar-coating mechanism. When tested in the lab and in animal models, the antibodies reactivated immune cells, which began attacking cancer cells. Tumours in treated mice grew significantly slower than in untreated controls.
The team is now refining the antibody for human use and planning early safety and dosing studies. They are also combining it with existing chemotherapy and immunotherapy and developing a companion test to identify patients whose tumours rely on this sugar-based pathway. Abdel-Mohsen estimates that if progress continues as planned, such a therapy could reach patients in around five years.
Beyond pancreatic cancer, the findings could have wider implications. The team is exploring whether the same sugar-coat trick is used in other hard-to-treat cancers and in non-cancer diseases where the immune system is misled. This research is just the beginning, and the team at Northwestern is poised to turn these sugar-based insights into real treatments for cancer, infectious diseases, and aging-related conditions.
