Susanna F. Greer: This researcher took a note from Katy Perry

Susanna F. Greer shared an article on LinkedIn:

“Imagine your DNA as a delicate thread.

If it breaks, your cells have two ways to fix it.

One is like quickly patching the thread with a rough knot, and the other is carefully sewing the ends back together. The protein 53BP1 acts like a gatekeeper, deciding which method to use.

Normally, 53BP1 favors the quick patch, blocking the careful sewing process.

In certain cancers, like those with BRCA1 mutations (like some ovarian and pancreatic cancers), losing 53BP1 can make tumors resistant to a specific type of treatment called PARP inhibitors (PARPi).

These treatments work best when the careful sewing process is blocked, so losing 53BP1, which promotes the rough patch method, can allow the tumor to grow despite treatment.

The V Foundation Grantee Dipanjan Chowdhury and team at Dana-Farber Cancer Institute Inc made a surprising discovery:

In certain cancers, patients with lower levels of 53BP1 actually had better survival rates. This was confusing because 53BP1 plays a key role in DNA repair, which should be crucial for keeping cells healthy.

So, the team wanted to know: why would less of it lead to better outcomes?

The answer they published in this cool paper seems to lie in how the immune system reacts. Without 53BP1, the DNA damage might be ‘messier’, creating signals that attract the immune system’s attention. The body’s immune cells – think of them as a SWAT team – are more likely to notice these signals and attack the tumor.

Dr. Chowdhury found that tumors with low 53BP1 levels had more active immune cells. They also showed higher levels of a protein which acts as a checkpoint in the immune system.

This might explain why these tumors respond better to treatments that block these checkpoints.

There haven’t been specific trials yet to test this idea, but the findings are incredible because they suggest that combining PARP inhibitors with immune therapies could be especially effective in treating cancers that have lost 53BP1.

This could be a game-changer for patients with these types of tumors, offering a new way to overcome resistance to existing treatments.

Finally, and the reason I think this paper is extremely cool – Dr. Chowdhury and team show that 53BP1’s role is unique.

This makes it a promising target for future treatments, especially in cancers that have been resistant to other therapies. Developing new ways to inhibit 53BP1 might help turn ‘cold’ tumors (those that usually evade the immune system) into ‘hot’ ones, making them more susceptible to immunotherapy.

So, 53BP1 isn’t just important for DNA repair, it also plays an important role in how the immune system interacts with tumors.

By understanding this relationship, researchers like Dr. Chowdhury and others can develop new strategies to treat cancers that are currently difficult to manage.

You can find the Chowdhury lab here and read and read the paper here.”

Source: Susanna F. Greer/LinkedIn

Susanna F. Greer is the Chief Scientific Officer at the V Foundation. Before this role, Dr. Greer was a Senior Scientific Director at the American Cancer Society, where she led the Biochemistry and Immunology of Cancer Research Program. Greer’s work focuses on identifying crucial signaling pathways in the immune response to cancer and has led to significant discoveries in molecular immunology and new epigenetic targets.