Killing breast cancer cells in a way that trains the immune system to recognize and destroy residual cancer cells could offer longer-lasting protection for people with the disease, according to new research funded by Breast Cancer Now.
The early-stage discovery was published today [23 May] in the journal Immunity, shows that by causing cancer cells to undergo a process called immunogenic cell death, the immune system is activated and alerted to disease in the body.
In order to induce this type of cell death, scientists at the Institute of Cancer Research in London targeted a protein called RIPK1, which plays a vital role in helping cancer cells survive and remain undetected in the body.
The team, based at the Breast Cancer Now Toby Robins Research Center at The Institute of Cancer Research (ICR), used a new and innovative technology called proteolysis targeting chimera (PROTAC) to successfully knock down RIPK1 in human cancer cells.
Through a process known as targeted protein degradation, PROTAC eliminates specific unwanted proteins within cells that were previously not ‘needed’. While traditional inhibitor drugs simply block the function of the protein, this process completely destroys the problematic protein.
Getting rid of RIPK1 triggers immunogenic cell death and mobilizes the immune system to destroy any remaining cancer cells that have evaded treatment or become drug-resistant.
The researchers also demonstrated in mice that targeting RIPK1 boosts immune system activation after radiation and immunotherapy treatment, enhancing the overall response to treatment and potentially offering longer-lasting protection against the disease as the body learns to recognize and kill cancerous cells. cells.
These early findings suggest that this approach could be effective for a range of different cancers, including triple-negative breast cancer, which can be more difficult to treat and is also more likely than most other breast cancers to return or spread within five years of diagnosis.
Professor Pascal Meier, Professor of Cell Death and Immunity at the Institute of Cancer Research, London, said:
“While all treatments aim to kill cancer cells, doing so in a way that activates the immune system to detect and kill any remaining cancer cells could make the treatment more effective and potentially give people a longer-lasting immune response against breast cancer.
“We know that RIPK1 plays a critical role in helping cancer cells stay alive and avoid detection by the immune system. Using this targeted protein degradation technology, known as PROTAC, we were able to use the cell’s own recycling system to specifically degrade and destroy the cancer protein RIPK1.
“Our exciting findings suggest that targeting RIPK1 could improve the effectiveness of existing cancer treatments and protect people from breast cancer recurrence by training the immune system to recognize and destroy cancer cells.”
Dr Simon Vincent, director of research, advocacy and advocacy 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 therapies for breast cancer that also have the potential to deliver a longer-lasting immune response against the disease.
“With one person dying from breast cancer every 45 minutes in the UK, research discoveries like these are urgently needed.”
Paula Glover, 45, from Surrey, was breastfeeding her 4-month-old baby in May 2012 when she found a lump. After an ultrasound and biopsy, Paula received the devastating news on her son’s 6 month birthday that she had triple negative breast cancer.
In the following months, Paula underwent surgery to remove 3 lymph nodes, 6 rounds of chemotherapy and a double mastectomy with reconstruction with lymph node drainage.
Paula eventually finished treatment and began to rebuild her life. She was on extended maternity leave to aid her recovery and returned to work as a professional psychologist in April 2013.
Almost ten years later, Paula found another lump and was diagnosed with breast cancer for the second time in December 2021.
After recovering from breast cancer, there is always the fear of recurrence. But after reaching almost 10 years cancer-free, I really thought I might be in the clear.”
Paula Glover
Paula’s treatment began the following January with more surgery, chemotherapy and radiotherapy. She completed her treatment in September 2022.
Having experienced a local recurrence of breast cancer, Paula is passionate about supporting any research that could provide long-term protection against the disease.
Paula added: “The anxiety about breast cancer coming back never goes away. Any aches and pains or rash is a concern. Knowing that new treatments are being developed that could keep cancer at bay for longer gives me hope that there may be more options and less stress for people like me in the future.”
Source:
Journal Reference:
Mannion, J., et al. (2024). A RIPK1-specific knockdown PROTAC achieves potent antitumor activity by enhancing immunogenic cell death. Immunity, immunity. doi.org/10.1016/j.immuni.2024.04.025.
