The Agora talk, Infectious Agents and Cancer featured two Nobel Laureates, who were able to demonstrate, after many years of research and rejections from the scientific community, that viruses and bacteria can cause cancer. Harald zur Hausen received the Nobel Prize in Physiology or Medicine in 2008, “for his discovery of human papilloma viruses causing cervical cancer.” Barry J. Marshall was awarded the Nobel Prize in Physiology or Medicine in 2005, along with J. Robin Warren, “for their discovery of the bacterium Helicobacter pylori and its role in gastritis and peptic ulcer disease.”
Over 20 percent of cancers are the result of an infection, but the infectious agents (viruses, bacteria or parasites) do not cause cancer on their own. The cancer surfaces after genetic modifications, and this may take decades. The link between infectious agents and cancer is still an area of interest for Harald zur Hausen. For the past decade, he has studied the influence of red meat consumption, particularly Eurasian dairy cattle, on the incidence of colon and breast cancers. During his lecture, zur Hausen discussed recent findings, where bovine meat and milk factors, infectious agents resembling plasmids, are found in the tissues of colon cancer patients. These factors cause chronic inflammation, which may lead to polyps, the precursor to colon cancer. Harald zur Hausen also explained the many protective aspects for babies after prolonged breastfeeding, which may reduce the risk for several acute and chronic diseases such as arteriosclerosis, multiple sclerosis, diabetes type 1 and 2, acute infections such as those caused by rotavirus, as well as leukemia, breast, colon, lung and ovarian cancer.
The Cancer-Causing Bacterium
Barry J. Marshall began his talk by introducing a little-known fact: in 1930, gastric cancer was the most common cancer in the US and Europe. Infection with Helicobacter pylori was and is one of the leading causes of gastric cancer, but an important factor contributing to the decrease of incidence rates was the widespread use of refrigerators in homes after 1930, which improved diets with fresh fruit and vegetables.
Helicobacter pylori lives in crevices of the gastric epithelium, a thin layer of cells lining the stomach. The bacteria separate the cells, causing them to leak, which may cause ulcers. Stomach acid protects the stomach from cancers, but H. pylori survives very well in acid and is present in the stomachs of approximately 50 percent of the world’s population. In most people, the bacteria do not cause any symptoms, especially if high acid secretion is maintained in the stomach. Eradication of H. pylori prevents 50 percent of gastric cancer. Marshall gave listeners some dietary advice regarding gastric health: “Fresh fruit and vegetables and an adequate amount of protein is important … and maybe not so many barbecues with carcinogens …”
The 70th Nobel Laureate Meeting is the first meeting for James P. Allison, who won the Nobel Prize in Physiology or Medicine in 2018, together with Tasuku Honjo, “for their discovery of cancer therapy by inhibition of negative immune regulation.” During his lecture, Allison focused on the current outcomes of years of basic science, drugs that can cure cancer. The therapy, now known as immune checkpoint blockade, uses the immune system to attack cancer cells. In the 1990s, Allison studied a T-cell protein, CTLA-4, which inhibits the response of T cells, key players in the immune system. Allison hypothesized that using an antibody to block the function of CTLA-4 would generate an immune response and kill cancer. The approach worked in the very first laboratory experiment; mice injected with anti-CTLA-4 were cured of cancer. As Allison wrote in his Nobel biography, “It was astounding. By blocking a single molecule, CTLA-4, we had reversed tumor growth and death!” It was a eureka moment, but it would take 17 years until the drug, ipilimumab, would become widely available to those who needed it.
“We know that checkpoint blockade works,” said Allison, but he admitted that it doesn’t work against all tumors. Anti-CTLA-4 therapy works best in melanoma, with a stable survival rate of 21 percent even 10 years post-treatment. Prostate and pancreatic cancers appear to be the hardest to tackle, due to the lack of immune cell infiltration in tumors, so-called “cold tumors”. One approach is to combine anti-CTLA-4 with hormonal therapy, turning cold tumors into hot ones, which are more susceptible to treatment. While there are thousands of ongoing clinical trials of new cancer drugs, combination therapy is a promising procedure for moving the survival rate up. Allison summed up his lecture by saying that the progress in cancer treatment has been amazing, and the outlook after diagnosis has changed even in the last 5 years.