Can Smoking and Its Resulting Carbon Monoxide Exposure Improve Cancer Treatment Outcomes?

By: Erin Hunter

Carbon monoxide (CO) is known to be lethal, but new research suggests it might also be able to improve treatment outcomes in some cancers. Investigators from the University of Iowa developed a drinkable, CO–infused foam that, when delivered to human cancer cells alongside an autophagy inhibitor, improved the effectiveness of the inhibitor. These findings were published in Advanced Science.1

Cancer can promote autophagy, a cellular process akin to a recycling system.1 During autophagy, cells are degraded and their cell parts are recycled by the body. It is an essential process because it helps maintain cellular health and prevent the buildup of damaged proteins.2

Unfortunately, cancer cells can survive and grow in a state of autophagic flux, and previous research findings suggest that autophagy occurs more often in cancer cells than it does in healthy cells. With this in mind, some researchers have posited that inhibiting autophagy could reduce cancer cell proliferation.1,2

In previous clinical trials, these autophagy inhibitors worked for some patients but not others, which renders their efficacy inconclusive, senior study author James Byrne, MD, PhD, University of Iowa assistant professor of radiation oncology and biomedical engineering, said in a press release.1 Upon reviewing these studies, investigators observed that smokers responded better to autophagy inhibitors than nonsmokers, Byrne said. In these trials, individuals who smoked and were treated with an autophagy inhibitor had a significant reduction in target lesion compared with nonsmokers.1,2 This is believed to be because smoking is associated with increased levels of CO.

“While we definitely don’t recommend smoking, this suggested that elevated carbon monoxide might improve the effectiveness of autophagy inhibitors,” Byrne said. “We want to be able to harness that benefit and take it into a therapeutic platform.”1

During the current study, investigators created a preclinical model to understand the anticancer effects of CO when combined with an autophagy inhibitor. The team fed CO-infused foam to mice that were being treated with an autophagy inhibitor for pancreatic cancer. Administration of these 2 agents significantly reduced tumor growth and slowed cancer progression in the mice.1,2 According to the study findings, 225 parts per million of CO increased the cytotoxicity of autophagy inhibitors, and it was more effective than treatment with CO or an autophagy inhibitor alone, according to authors of the paper.2

Investigators also tested the drinkable CO and autophagy inhibitor combination on human prostate, lung, and pancreatic cancers in vitro, where they observed similar antitumor effects.1

“Given that the combination of CO with autophagy inhibitors was effective in treating both prostate and pancreatic cancers in our model systems, it will likely be applicable to a wide variety of malignancies,” authors wrote in the paper.2

Although CO induces autophagy in cancer cells, autophagy inhibitors might work better in an environment with higher CO, such as in an active smoker. Therefore, when an autophagy inducer was paired with an autophagy inhibitor, it had a synergistic anticancer effect.2

Investigators add that CO can be anti-inflammatory, meaning that it could be beneficial when administered alongside therapies such as radiation therapy, which causes tissue injury, according to the paper’s authors.2 Moreover, the process of administering CO could inspire the use of GEM to administer other agents in a variety of combination therapies, although there still needs to be more prospective studies evaluating the anticancer benefits of CO-infused products and autophagy inhibitors.2

Ultimately, this therapeutic combination opens “a promising new approach that might improve therapies for many different cancers,” said Byrne.1

REFERENCES

1. Brown J. Drinkable, carbon monoxide-infused foam enhances effectiveness of experimental cancer therapy. Carver College of Medicine. January 10, 2024. Accessed March 12, 2024. https://medicine.uiowa.edu/content/drinkable-carbon-monoxide-infused-foam-enhances-effectiveness-experimental-cancer-therapy

2. Bi J, Witt E, McGovern MK, et al. Oral carbon monoxide enhances autophagy modulation in prostate, pancreatic, and lung cancers. Adv Sci (Weinh). 2024;11(9):e2308346. doi:10.1002/advs.202308346