New way to kill cancer cells could lead to longer lasting protection for people with breast cancer

Killing breast cancer cells in a way that trains the immune system to recognize and destroy residual cancer cells could offer longer lasting protection to people with the disease.

The early stage discovery published in the journal Immunity, shows that by causing cancer cells to undergo a process called immunogenic cell death, the immune system is switched on and becomes alert to the disease in the body.

In order to bring about this type of cell death, scientists at The Institute of Cancer Research, 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 in the Breast Cancer Now Toby Robins Research Center at The Institute of Cancer Research (ICR) collaborated with scientists at the ICR’s Center for Cancer Drug Discovery and Center for Protein Degradation. They used a new and innovative technology called proteolysis targeting chimera (PROTAC) to successfully destroy RIPK1 in cancer cells.

Targeted protein degradation

Through a process known as targeted protein degradation, PROTAC eliminates specific unwanted proteins within cells that have previously been “undruggable.” While traditional inhibitor drugs merely block the function of the protein, this process destroys the problem protein entirely.

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 resistant to drugs.

Researchers demonstrated that targeting RIPK1 enhances immune system activation after radiotherapy and immunotherapy treatment in mice, boosting overall response to treatment and potentially offering longer lasting protection against the disease as the body learns to recognize and kill cancer 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 harder to treat and is also more likely than most other breast cancers to return or spread within five years following diagnosis.

Professor Pascal Meier, Professor of Cell Death and Immunity at The Institute of Cancer Research, London, said, “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.

“Our exciting findings suggest that targeting RIPK1 could improve the effectiveness of existing cancer treatments and protect people from recurrences of breast cancer, by training the immune system to recognize and destroy cancer cells.”

Professor Swen Hoelder, Professor of Medicinal Chemistry and Drug Design and Head of Chemistry within the Center for Cancer Drug Discovery at The Institute of Cancer Research, London, said, “We made this discovery through a fantastic collaboration between different scientists across the ICR.

“Drug discovery scientists within the ICR’s Division of Cancer Therapeutics worked with cancer biologists to see a concept through from fundamental discovery science to an active drug discovery project, resulting in the development of a PROTAC degrader which could keep people’s cancer at bay for longer.

“This study further demonstrates how targeted protein degradation can be used to attack cancer. The ICR has been pioneering this innovative technology for some time—and we continue to do so through our dedicated Center for Protein Degradation.

Dr. Simon Vincent, director of research, support and influencing at Breast Cancer Now, 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 U.K., research breakthroughs like these are urgently needed.”