Heart disease and cancer are the top causes of death in the United States, yet it is uncommon for cancer to develop in the heart.
This phenomenon has puzzled clinicians, although they have been thankful for it. A paper published Thursday in Science offers a potential explanation: the heart’s constant beating and blood-pumping activity creates a hostile environment for cancer cells. Although the study was conducted in mice and is preliminary, experts suggest it could lead to new cancer treatment strategies.
“It’s interesting that [cancer] doesn’t occur that often in the heart. People have not really been sure exactly why, but it’s just something that we accepted. What makes this article really fascinating is that they have provided a potential mechanism to explain this phenomenon,” said Michael Fradley, a professor of clinical medicine at University of Pennsylvania who was not involved with the study.
It seems counterintuitive that the heart would resist metastatic cancers, given that cancer cells travel through the bloodstream. “This is certainly incredibly interesting — it’s hypothesis generating, which is exciting, and I’m really enthusiastic about the foundation that this creates for future studies,” Fradley said.
Heart cells are known to have limited regenerative abilities, which poses challenges for heart failure patients. Researchers hypothesized that this inability to regenerate might prevent cancer, which thrives on uncontrolled cell growth, from originating in the heart. Even when cancer metastasizes to the heart, the resulting tumors are often smaller than those in other organs.
The study, led by Giulio Ciucci and Serena Zacchigna from the International Centre for Genetic Engineering and Biotechnology in Trieste, Italy, explored the connection between mechanical stress and cancer resistance. This was inspired by previous observations that cellular regeneration occurs in patients with a left ventricular assist device, which alleviates heart pressure.
To investigate, researchers conducted an experiment where they transplanted a second heart into mice, which did not pump blood through the left ventricle. Cancer cells were injected into both hearts, and it was observed that cancer spread more rapidly in the transplanted heart, which experienced less stress, while it was rare in the native heart.
The researchers also identified genetic differences between cancers that could spread in the heart and those that could not, highlighting a protein that senses mechanical forces and suppresses gene activity related to cancer cell proliferation. “What’s really striking is this link they provide between mechanical load and epigenetic regulation. They show that these physical forces can directly alter gene expression in cancer cells, which is a powerful concept that extends beyond cardiology,” said Javid Moslehi, a cardiologist at the University of California, San Francisco, who was not involved in the study.
The research opens a potential treatment avenue using machines to apply pressure to cancer cells, mimicking the heart’s rhythmic beating. Zacchigna, a molecular biologist and physician, noted that they are working with engineers to develop devices that could apply pressure to surface-level cancers, such as those in the skin or breast.
“We have the first prototypes, and results are promising,” she said, expressing hope that this therapy could enhance other treatments. “Other than adding this mechanical stimulus, it is a way to perform a kind of massage the tumor that could improve the delivery of any chemo or immunotherapy.”
CORRECTION: An earlier version of this story incorrectly stated Michael Fradley’s university affiliation. It has been corrected.
