Colon cancer's 'big bang' moment reveals the shape of the disease

Like the astronomical explosion that started the universe, bowel cancer has a 'big bang' moment that determines how it grows, according to a new study by scientists funded by Cancer Research UK and the Wellcome Trust.

Researchers from the Institute for Cancer Research in London, the Human Technopole Foundation in Milan, and Chalmers University of Technology in Sweden have discovered that the “big bang” moment in colorectal cancer is caused by cancer cells successfully hiding from the immune system, a process called immune escape.

During this process, intestinal cancer cells destroy genes that allow the immune system to detect the cancer. Since the point of immune escape, scientists have observed very limited changes in how cancer manifests itself in the immune system.

This study provides a possible way for doctors to identify. people with colon cancer Who is likely to respond? immunotherapyincluding colon cancer vaccines designed to help the immune system recognize and destroy cancer cells.

Professor Trevor Graham, Professor of Genomics and Evolution and Director of the Center for Evolution and Cancer at the London Institute of Cancer Research, said:

“Some colon cancers are 'born bad'; how they interact with the immune system is set early on.

“Immunotherapies and bowel cancer vaccines hold great promise in treating this disease. Our study suggests that the relationship between colorectal cancer and the immune system does not change significantly as the patient grows older. If we can target that relationship early, we should increase the chances of successful treatment.”

“As colorectal cancer treatments become increasingly individualized, understanding how tumors evolve and change is even more important than ever. Like the explosion that determined the course of the universe, colorectal cancer's Big Bang gives us our greatest clues about what its future will be and how we can change that future.”

Bowel cancer is the fourth most common cancer in the UK, with around 44,100 new cases in the UK each year and around 120 new cases every day. It is known that approximately 15% of colorectal cancers respond well to immunotherapy, while the remainder are less likely to respond to this type of treatment.

Several therapeutic colorectal cancer vaccines are currently in clinical trials. It is designed to train the immune system to recognize and destroy newly appearing bowel cancer cells to prevent bowel cancer from coming back after initial treatment.

“This is a very important finding,” said study lead author Esther Lakatos, a mathematical biologist at Chalmers University of Technology and the University of Gothenburg in Sweden.

“Our research group has investigated and found answers to how cancer cells become unrecognized by the immune system. Our hope is that these insights will eventually lead to more targeted and effective early treatments in addition to surgery.”

In the study, scientists analyzed colon cancer immune cells and cancer cell tissue taken from 29 people. They generated complete DNA and RNA sequences and looked at how tightly the DNA was wrapped around proteins in chromosomes (known as chromosomes). epigenetics).

Scientists have discovered that cancer cells can evade the immune system through epigenetic changes that change the way DNA is “read” to make RNA, the instructions for making proteins.

In cancer, these changes affect the number of neoantigens (“danger signal” proteins that attract immune cells) that appear on the surface of cancer cells. When there are fewer neoantigens, it becomes harder for the immune system to recognize and destroy cancer.

Scientists believe that combining immunotherapy with epigenome-modifying drugs may make immunotherapy more effective for patients with colorectal cancer because the cancer produces more neoantigens that can be targeted by the immune system. Further research is needed to validate this idea before clinical trials in patients can begin.

For everyone to overcome colon cancer, we need to understand what happens in the very early stages of the disease. No matter how different colorectal cancer tumors may look, one critical moment at the time of initiation can make a big difference in how the cancer grows.

Colorectal cancer has an insidious nature that resists treatment. Immunotherapy is starting to work for some patients, but it doesn't work for everyone. This study not only helps us understand why, but also provides new insights into improving the effectiveness of immunotherapy for colorectal cancer. ”

Dr Catherine Elliott, Director of Research at Cancer Research UK

Tom Collins, Research Leader, Discovery Research, Wellcome Trust, said:

“By tracking the early stages of colorectal cancer, the research team has shed valuable new light on mechanisms that may lead to more targeted and effective early treatments.

“This is a powerful example of discovery science. This molecular-level research provides a deeper understanding of how colorectal cancer develops and may lead to improved health outcomes for patients in the long term.”

The paper, titled “Epigenetic drives and early immune evasion in the evolution of colorectal cancer,” was published today (5 November). natural genetics.