Potential new breakthroughs in liver cancer research

  In the struggle between humans and disease, the latter usually prevails in the end. For patients with advanced disease, the pace of biomedical research is very slow. It takes years—other decades—to understand how the disease spreads in the body and develop a drug to treat it. Then, before the drug is approved for human clinical trial research, it will take countless years to test it in laboratories and animal experiments. Before drugs were developed, millions of people lost their lives due to HIV/AIDS.

  Therefore, if a research breakthrough can bring more direct relief to patients, it will be very exciting. Recently, Arlin Rogers, associate professor of pathology at Tufts University’s Cummings School of Veterinary Medicine, made such a breakthrough in liver cancer research. They found that prolactin, a hormone that helps lactating mothers produce milk, can help Prevent this disease.

  Liver cancer is relatively rare in the United States, while lung, breast, prostate and colorectal cancer are the most commonly diagnosed cancers. However, according to the World Health Organization (WHO) data, liver cancer is the second leading cause of cancer death after lung cancer worldwide. The disease is particularly prevalent in Southeast Asia and sub-Saharan Africa, where liver cancer is related to hepatitis B and C viruses, and toxins in food and water supplies.

  The number of patients with liver cancer in the United States is also increasing, especially before hepatitis C was discovered in the 1970s and 1980s and blood donors were routinely tested. Those who received blood transfusions might develop liver cancer. Rogers said: "Many hemophiliacs die from hepatitis C. Now these patients are suffering from chronic liver disease, which can progress to cirrhosis and then cancer. Patients with obesity and type 2 diabetes can also develop chronic liver disease. This increases the risk of cancer."

  When Rogers, Ph.D. of Experimental Pathology, was working as a researcher at MIT, he began to study liver cancer. At that time, a strange phenomenon aroused his interest. In all mouse liver cancer studies, researchers only use male mice. Rogers said: "That is because the prevalence of male mice is higher, so it is cheaper to use only male animals. It seems that no one is interested in understanding why this is the case."

  Pituitary gland prescription

  In humans, liver cancer is more common in men. According to data from the World Health Organization, according to different countries, men are two to eight times higher than women. Diseases that disproportionately affect men, such as cardiovascular disease, share a common chronic inflammatory state. In this state, the body's immune response causes tissues to be filled with blood cells and chemicals. Rogers believes that liver cancer may also be the case.

  But what affects the varying degrees of inflammation between men and women? The obvious answer seems to be sex hormones such as testosterone and estrogen. However, when Rogers reviewed the scientific literature, he found proof in a humble paper in the 1940s that the root may lie in different areas of the body: the pituitary gland, which releases growth hormone and prolactin.

  In the laboratory, Rogers and colleagues exposed liver cells to pituitary hormones. Growth hormone has little effect; however, prolactin can significantly inhibit certain inflammatory reactions. Based on this surprising discovery, Rogers speculated that prolactin may play a role in protecting women from liver cancer. He said: "I think it's too simplistic to focus only on estrogen and testosterone. This is not a story about sex hormones, this is a story about the pituitary gland."

  To test this hypothesis, Rogers conducted a series of mouse experiments, including using female and male mice that cannot produce prolactin. Female mice without the prolactin gene have a higher rate of cancer-75%, while only 10% of normal female mice with prolactin have cancer. It has an effect even in male mice, although it is not obvious-male mice with prolactin have a similar rate of cancer compared with male mice without prolactin, but only show about one-third of the tumors. He said: "I thought I would see effects in female animals, but I didn't expect to see a response in male mice. Prolactin can even help them."

  This discovery brings hope to human patients, because the US Food and Drug Administration has approved some drugs that can artificially amplify prolactin levels. These drugs, most commonly used for mental illness or gastrointestinal diseases, are sometimes used to promote milk production in primiparous cows with milk production problems. Rogers tested the drug in mice exposed to liver cancer-inducing chemicals. He found that only 22% of the male mice that took the drug had tumor shrinkage, compared to 100% of the mice that did not take the drug.

  Rogers published relevant research results in the recent "PNAS" magazine. He hopes that this research may one day help not only patients in the United States, but also people in developing countries. According to a World Cancer Fund survey, approximately 83% of liver cancer cases occur in developing countries.

  He said: "If the targets we found in mice also work in humans, we can ship drugs to Asia and Africa in the future. These drugs already exist and they have been approved. Obstacles will also be taken by doctors. Accept it with the patient.” At present, Rogers is working with statisticians at Tufts Medical School to determine whether patients who have taken these drugs for other diseases have a lower incidence of liver cancer.

  If the use of prolactin-inducing drugs as a treatment is successfully used in clinical trials, it may only take a few years, instead of the usual decades, before the drug can be used as a prescription drug for people at high risk of disease. Rogers said: "We don't think it will cure liver cancer, but it may help prevent it. History shows that the best way to reduce the burden of cancer is to prevent it from happening."