New treatment approach may provide longer-lasting protection for people with breast cancer

Killing breast cancer cells in a way that trains the immune system to recognize and destroy remaining cancer cells may offer longer-lasting protection for people with the disease, according to new research funded by Breast Cancer Now.

The early discovery, published in the journal Immunity, showed that by inducing a process called immune cell death in cancer cells, the immune system is activated and becomes more attentive to diseases in the body.

To induce this type of cell death, scientists from London's Institute of Cancer Research (ICR) targeted the protein RIPK1, which plays an important role in the survival of cancer cells and their ability to remain undetected in the body.

The team, based at ICR's Toby Robins Research Center at Breast Cancer Now, used a new and innovative technology called proteolysis target chimera (PROTAC) to successfully kill RIPK1 in human cancer cells.

Through a process known as targeted protein degradation, PROTAC eliminates specific unwanted proteins in cells that were previously considered “untreatable.” While traditional inhibitor drugs simply block protein function, this process completely destroys the problematic protein.

Killing RIPK1 causes immune-mediated cell death and mobilizes the immune system to destroy any remaining cancer cells that have escaped treatment or become drug-resistant.

The researchers also demonstrated in mice that targeting RIPK1 enhances immune system activation after radiotherapy and immunotherapy, increasing overall treatment response and potentially offering longer-lasting protection against disease as the body learns to recognize and destroy cancer cells.

These early results suggest the approach may be effective for a number of different cancers, including triple-negative breast cancer, which is more difficult to treat and has a higher chance of recurrence or spreading within five years of diagnosis.

Professor Pascal Meyer, Professor of Cell Death and Immunity at the London Institute of Cancer Research, said:

“Although all therapies aim to kill cancer cells, doing so in a way that activates the immune system to find and destroy any remaining cancer cells can make treatment more effective and potentially offer people a longer-lasting immune response to breast cancer.

p>

We know that RIPK1 plays an important role in the survival of cancer cells and their ability to evade detection by the immune system. Using targeted protein degradation technology known as PROTAC, we were able to use the cells' proprietary recycling system to specifically degrade and kill the RIPK1 protein in cancer cells."

Dr Simon Vincent, director of research, support and impact at Breast Cancer Now, which funded the study, said:

“There are many hallmarks of cancer, including the ability of cancer cells to evade detection by the immune system and resist destruction by conventional treatments such as chemotherapy.

However, these exciting results may pave the way for new targeted treatments for breast cancer that may also offer a longer-lasting immune response to the disease.