Tumors release signals that affect a body’s repair response

In surprising breakthrough, scientists in Israel find cancer may help heal the failing heart

A study by researchers at the Technion finds that injecting cancerous serum in mice decreased cardiac fibrosis, paving the way for innovative therapies

A discovery by Prof. Ami Aronheim and his team at the Technion–Israel Institute of Technology shows that the growth of cancerous tumors may actually combat cardiac dysfunction and reduce fibrosis, the scarring process that stiffens the heart muscle.

“The failing heart can beat much better in the presence of cancer cells or a tumor,” said lead investigator Aronheim, dean of the Technion’s Ruth and Bruce Rappaport Faculty of Medicine, speaking to The Times of Israel.

“This is very surprising,” Aronheim said.

Currently, no drugs exist that can reverse fibrosis or improve the heart muscle once it has been damaged, he explained.

The new findings could open the door to the development of innovative and groundbreaking therapeutic approaches.

PhD students Lama Awwad and Laris Achlaug led the research, which was recently published in JACC: CardioOncology, a peer-reviewed journal of the American College of Cardiology.

Heart disease and cancer are the two most significant causes of death in Israel, according to the Health Ministry. While they have been considered separate diseases, researchers now confirm that they are highly connected — and they affect each other’s outcomes.

The diseases also share similar risk factors, including smoking, obesity, diabetes, environmental factors and aging.

“These are two diseases that are all around us, and that people we know suffer from,” Awwad, 28, told The Times of Israel in a recent Zoom interview together with Achlaug.

Moreover, Awwad said, the two conditions share similar mechanisms, which involve inflammation, growth signals, and survival.

Heart disease is a cancer-spreader

In research conducted by Aronheim’s lab five years ago, the scientific team found that a stressed heart can actually accelerate the growth and spread of cancer.

“When we first looked at how heart failure affects cancer, we showed that a damaged heart can make the cancer more aggressive and more metastatic,” Aronheim said.

This can happen because cytokines, chemical messengers that immune cells use to communicate with one another, are released by the heart. These cytokines promote the growth and spread of cancer cells.

However, while doing these experiments, the researchers noticed an unexpected — and inverse — result. In tumor-bearing mice, heart failure was “much less pronounced.”

“This led us to start to think about studying the other direction, how cancer affects heart failure,” Aronheim said.

The scientists implanted cancer cells in mice with heart failure.

“We were surprised to find an improvement not only in the ability of the mice’s hearts to pump blood but also an improvement in the muscular system,” said Achlaug, 31. “It was very motivating.”

Moreover, the extent of fibrotic, or scarred, tissue was significantly decreased in a short period of time.

“This was a breakthrough for us,” Aronheim said. “Of course, it was clear to us that it’s not a possible treatment to use another disease for the sake of repairing heart dysfunction. So we had to study the mechanism.”

The researchers hypothesized that exposing immune cells to cancer cells can yield a process called “immunomodulation,” which enables the immune system to regenerate and begin fighting inflammation.

To test their hypothesis, the scientists injected serum extracted from the blood of the tumor-bearing mice into heart-diseased mice. These mice exhibited rapid improvements in cardiac function and reduced fibrosis.

The researchers analyzed the molecules in the serum and found that the cytokines were released from natural killer cells, also known as NK cells. These are a type of immune cell that attacks foreign cells when activated.

The cytokines activated macrophages, a type of white blood cell that plays a crucial role in consuming pathogens. The cytokines helped reprogram the macrophages into anti-inflammatory, healing-focused cells.

The work of Aronheim’s lab has shed light on the common biological pathways between cancer and heart disease, said Izhak Kehat, head of the department of physiology, biophysics, and systems biology, in the Technion’s Faculty of Medicine, who was not involved in the project.

“Tumors can release signals that affect the whole body’s repair and immune response,” Kehat said. “And some of these signals can be harnessed to improve heart disease.”

Awwad said the research team has a patent on the serum with “a cocktail of positive factors.”

“We have to test its toxicity and prove that it’s safe to use,” Achlaug explained.

Breaking down social — and scientific — barriers

Awwad, who lives in Tamra, an Arab town in the Galilee, and Achlaug, who lives in Kfar Kama, a Circassian town 60 kilometers (37 miles) away, spoke about their challenges as researchers and as mothers of small children.

They credited their husbands, who are both engineers (Awwad’s husband works at Google and Achlaug’s husband works at Apple), and “who can sometimes work from home during the week,” Achlaug said.

“And also when we take our work home on weekends,” Awwad added.

She noted that approximately 50 percent of the Technion’s graduate students are women, and about 50% of those are Arabs. However, she said there are few female researchers because of the “long hours we spend in the lab.”

In the Circassian community, which numbers 5,000 in Israel, Achlaug said there are only two other women who have PhDs.

When they attend scientific conferences abroad, Awwad said that people are less curious about them as women and more interested in their lives as Arabs in Israel.

“People ask me a lot of questions about ‘what’s really happening,'” Awwad said. “It’s good because I like to calm them down.”

Achlaug said they never encountered hostility at conferences, but she was “a little nervous” when presenting her paper to a group of scientists from Beirut.

“But there’s a sense of honor among researchers to focus on science,” she said.

“Then, afterwards,” Awwad said, “they can have their opinions.”