Could a single drug treat the two leading causes of death in the United States: cancer and cardiovascular disease?

What do you think are the two biggest killers in the world? Based on media coverage, you may have suspected gun violence, accidents, or COVID-19. But the two most common causes of death are cardiovascular disease and cancer. These two diseases together account for nearly 50% of deaths in the United States

On the surface, cardiovascular disease and cancer appear to be very different. But newly discovered parallels between the origins and development of these two diseases mean that some treatments may be effective against both.

I'm a biomedical engineer who has spent two decades researching and developing ways to make drugs move better through the body. It turns out that tiny, engineered nanoparticles that can target specific immune cells could be a way to treat cancer and cardiovascular disease.

Cardiovascular diseases and cancer

Atherosclerosis is the deadliest form of cardiovascular disease. It occurs due to inflammation and the buildup of fat, cholesterol and other lipids in the blood vessel wall, forming plaque. Most heart attacks are caused by plaque rupture. The body's attempt to heal the wound can result in the formation of a blood clot, which blocks the blood vessels and results in a heart attack.

On the other hand, cancer usually arises from genetic mutations that cause cells to divide uncontrollably. Unruly, rapid cell growth can be destructive if left untreated because it is difficult to stop without damaging healthy organs. Cancer can arise and occur in any organ of the body.

Although cardiovascular disease and cancer appear to have different origins and causes, they share many common risk factors. For example, obesity, smoking, chronic stress and certain lifestyle choices such as poor diet are linked to both diseases. Why might these two diseases have similar risk factors?

Many of the similarities between cardiovascular disease and cancer can be attributed to inflammation. Chronic inflammation is a leading cause of atherosclerosis, as it damages the cells that line blood vessels and progressively worsens plaques. Likewise, chronic inflammation can trigger cancer through the increase in mutations and promote the survival and spread of cancer cells by increasing the growth of the blood vessels that supply them with nutrients and suppressing the body's immune response.

Treat two diseases at the same time

Research suggests that cancer therapies may also help treat atherosclerosis.

One example is drugs that target immune cells called macrophages in tumors and cause them to eat cancer cells. It turns out that a similar drug can cause macrophages to eliminate dead and dying cells in atherosclerosis, thereby shrinking plaques.

Another example is antiglycolytic therapies, which prevent the breakdown of glucose. Glucose or sugar is the body's main source of energy. These drugs can make diseased tumor blood vessels and atherosclerotic blood vessels appear more “normal” and essentially reverse the disease process in these vessels. They can also reduce inflammation in atherosclerosis.

Although currently marketed treatments such as statins and fibrates can reduce lipid levels and blood clotting in atherosclerosis, these drugs have not adequately addressed the risk of death from cardiovascular disease. To improve outcomes, doctors are increasingly using multiple medications directed at different targets. An interesting class of treatments are sodium-glucose cotransporter-2 inhibitors, traditionally used to treat diabetes. Researchers have shown that these drugs provide significant protection against cardiovascular disease as well as treating cancer.

Clinical studies of statins and sodium glucose cotransporter-2 inhibitors indicate a close overlap between inflammation, metabolism and cardiovascular disease, suggesting new treatment options. One example is immunotherapies that “inhibit” immunity—that is, they remove the brakes that tumors place on the immune system. This approach to cancer treatment also reduced atherosclerotic plaques in animal studies and reduced vascular inflammation in a small human study.

A nanomedical Trojan horse

A recent discovery showed that nanotubes – a very small particle made of carbon over 10,000 times thinner than a human hair – can penetrate certain immune cells, move through the bloodstream and enter tumors as a Trojan horse. These nanotubes can carry whatever researchers put on them, including drugs and imaging contrast agents.

The immune cells carrying the nanotubes naturally penetrate tumors through the inflammatory response. Since cancer and atherosclerosis are inflammatory diseases, my research team and I investigated whether immune cells loaded with nanotubes could also serve as plaque transport vehicles.

Nanotubes can be loaded with a therapy that stimulates immune cells to “eat” plaque debris, thereby reducing plaque size. Additionally, limiting drug delivery specifically to these immune cells reduces the risk of off-target side effects. These nanotubes can also be used to improve the diagnosis of cardiovascular disease by highlighting plaques.

Another way nanoparticles can enter tumors is by passing through openings in new blood vessels created in inflammatory diseases. This is known as the enhanced permeation and retention effect, where larger molecules and nanoparticles accumulate in tissues with leaky blood vessels and remain there for some time due to their size. Researchers have used this effect, first discovered in cancer, to improve drug delivery for cardiovascular diseases, which can also cause leaky blood vessels.

Improving drug development

The shared molecular pathways of cancer and cardiovascular disease have important regulatory implications. The costs of transporting medication to the clinic are enormous. The ability to use the same drug in two different patient groups offers great financial and risk-reducing incentives. It also offers the possibility of treating patients with both diseases at the same time.

Nanoparticle-based cancer drugs first entered the clinic in 1995, and researchers have developed many more since then. However, there is currently only one cardiovascular nanomedicine approved by the Food and Drug Administration. This suggests the possibility of new nanotherapy approaches to improve the effectiveness of cardiovascular drugs and reduce side effects.

Because of the parallels between cancer and cardiovascular disease, cancer nanomedicines could be strong drug candidates to treat cardiovascular disease and vice versa. As basic research discovers further molecular parallels between these diseases, patients will benefit from better therapies that can treat both diseases.

This article was republished from The Conversation, a nonprofit, independent news organization that brings you facts and trusted analysis to help you understand our complex world. It was written by: Bryan Smith, Michigan State University

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Bryan Smith receives funding from the National Institutes of Health (the National Cancer Institute) and the Juvenile Diabetes Research Foundation. He has received funding from the American Heart Association, the American Association for Cancer Research, and the Ralph and Marian Falk Medical Research Trust.