Radioactive Bacteria used in Cancer Treatment
I’ve been meaning to write this post for ages now about research describing how radioactive bacteria was used to treat pancreatic cancer in mice. It sounds like science fiction, but it’s not; this was published last month in the Proceedings of the National Academy of Sciences journal by a research group in New York. See full text (open access).
• Pancreatic cancer typically has an extremely poor prognosis. It is known as a ‘silent killer’ because the disease develops surreptitiously, with general non-specific symptoms; by the time a positive diagnosis is made, the disease has usually progressed into more advanced stages where a cure is no longer an option.
• The spread of cancer, known as metastasis, is generally more ominous than the primary tumor itself. Our current medical arsenal is actually quite effective at eliminating primary tumors through traditional treatments such as surgery, chemotherapy and radiation. The reason cancer can be so deadly is because of its capacity to spread and form metastases, which tend to be more aggressive and resistant to treatment than the primary tumor.
• The tumor microenvironment is the cellular environment in which the tumor exists; it includes blood vessels, immune cells with their associated molecules, signaling molecules etc. The tumor microenvironment contributes to tumor initiation, progression, and response to therapy. Solid tumors such as pancreatic cancers often have an immunosuppressive tumor microenvironment; this means that there are cells within the tumor microenvironment that can suppress the activity of the immune system. Think of it as a wound that fails to heal.
• Listeria monocytogenes is a pathogen that reproduces inside the host cell, and can typically be cleared by the immune system in normal tissues. However, the disease is more serious in patients with compromised immune systems, such as people who take immunosuppressant drugs or those infected with HIV.
• Researchers in New York used these unrelated properties of solid tumors and Listeria to set up an ingenious experiment. First, they linked a radioactive isotope of the element Rhenium (Re) to a weakened strain of live Listeria. Next, they used this radioactive Listeria to infect mice that had metastatic pancreatic tumors. The reasoning behind this experiment was to use the ability of Listeria to infect immunocompromised tissues, such as those found in the tumor microenvironment, and target radiation therapy to it.
• The results were dramatic; the radioactive Listeria was able to infect and multiply within metastases, but not in normal tissues. The dose of radiation present in the metastases was also much higher than the levels found in normal tissues. Finally, the number of metastatic tumors and the tumor weight was reduced in radioactive-Listeria treated mice, compared to controls.
• The implications of these experiments are huge; as I said earlier, metastatic pancreatic cancer is typically a death sentence. These tumors cannot be removed surgically, and they are resistant to chemotherapy and external radiation. The use of chemotherapy can only extend survival by six months. The discovery that live weakened bacteria can deliver radioactivity directly to the metastatic tumors, without killing normal tissues is huge. It might herald an exciting new era in the treatment of metastases from pancreatic cancer, and possibly other solid tumors too.