Researchers, part-funded by Breast Cancer Now, discovered that killing breast cancer cells in a new way activates the immune system to detect and destroy remaining cancer cells. This could offer longer protection to people with the disease.
Testing a new technology
Professor Pascal Meier and his team at the Breast Cancer Now Toby Robins Research Centre at the Institute of Cancer Research, London targeted a protein called RIPK1. This protein plays a key role in helping cancer cells survive and remain undetected in the body.
They used a new and innovative technology called proteolysis targeting chimera (PROTAC) to successfully destroy RIPK1 in cancer cells.
PROTAC eliminates specific unwanted proteins within cells through a process known as targeted protein degradation. While traditional inhibitor drugs only block the function of the protein, this process destroys the unwanted protein entirely.
Triggering the immune system to help
Getting rid of RIPK1 triggers a process known as immunogenic cell death in cancer cells. This mobilises the immune system to destroy any remaining cancer cells that have escaped treatment or become resistant to drugs.
The researchers showed that targeting RIPK1 with this new technology activates the immune system after radiotherapy and immunotherapy treatment in mice.
This boosted the overall response to treatment and could potentially offer longer protection against the disease as the body learns to recognise and kill cancer cells.
While all therapies aim to kill cancer cells, doing so in a way that activates the immune system as well to detect and kill any remaining cancer cells could make treatment more effective and potentially offer individuals a longer-lasting immune response against breast cancer. We know that RIPK1 plays a crucial role in helping cancer cells stay alive and avoid being detected by the immune system. By using this targeted protein degradation technology, known as a PROTAC, we have been able to use the cell’s own recycling system to specifically degrade and destroy the RIPK1 cancer protein.
Professor Pascal Meier
Professor of Cell Death and Immunity at The Institute of Cancer Research, London
Offering long-lasting protection
The early-stage discovery shows that by causing cancer cells to undergo immunogenic cell death, the immune system is switched on and becomes alert to the disease in the body.
The researchers hope this approach could be effective for a range of different cancers, including triple negative breast cancer. Triple negative breast cancer can be harder to treat and is also more likely than most other breast cancers to return or spread within 5 years of diagnosis.
Dr Simon Vincent, director of research, support and influencing at Breast Cancer Now, which funded the research, said:
There are many hallmarks of cancer, including the ability of cancer cells to evade detection by the immune system and resist being killed by common treatments such as chemotherapy. However, these exciting findings could pave the way for new, targeted breast cancer treatments, which also have the potential to offer a longer-lasting immune response against the disease. With one person dying from breast cancer every 45 minutes in the UK, research breakthroughs like these are urgently needed.
Dr Simon Vincent
Director of research, support and influencing at Breast Cancer Now
This study was published in Immunity and funded by Breast Cancer Now and Cancer Research UK.