Finding Pancreatic Cancer's Kryptonite

I have spent a good portion of the past three months researching pancreatic cancer as part of this course. Over this period of time, I've learned so much about the causes, risks, treatments, and prognoses of the disease, and to be honest, the overall outlook is pretty bleak. 80% of patients die within a year a diagnosis, and 95% die within five years. The cancer itself is incredibly hard to detect, and according to The Hirschberg Foundation for Pancreatic Cancer Research, "fewer than 10% of patients' tumors are confined to the pancreas at the time of diagnosis." Metastatic tumors are even more detrimental to one's health, and are difficult to operate on- often requiring removal of surrounding organs' tissues.

However, recent development in treatment has shown extremely promising results, halting or shrinking the growth of tumors in a large percentage of patients. In many pancreatic cancer patients, chemotherapy resistance or immunity can develop as the result of a "immunosuppressive tumor microenvironment"- a small area surrounding the tumor inactivate the body's normal immune response in the area. Without T-cells to deter cancerous cells, tumors can grow unrestrained, often leading to metastasis and the other common symptoms of pancreatic cancer. Some leukocytes can even be altered by the tumor to essentially "hide" the mass from the body's immune system.

This new treatment utilizes a receptor protein on the surface of many macrophage defense cells, CD40. By combining a standard chemotherapy drug, gemcitabine, with a CD40-activating antibody, researchers were able to effectively redirect the T cells' attack back toward the tumor, and reduce growth. Patients utilizing this new treatment saw an average increase in post-diagnosis survival of nearly two months. For a disease with an average prognosis of around five months, a near 40% increase in survival is a big deal. Metastatic tumors, usually extremely difficult to treat, were also effectively shrunk via this treatment. Additionally, injecting tumor-ridden mice with just the CD40-activating antibody had anti-tumorgenic effects- reducing tumors in many of the rodents. This shows promise for combining this antibody with other chemotherapies, as well as other T cell activators (like those from the Tumor Necrosis Factor family of proteins, which CD40 belongs to) for even more effective treatment.

The published article doesn't talk much about the side effects or dangers of this method of treatment, outside of normal chemotherapy side effects. However, the mechanism by which it works raises concerns. If tumor cells are killed by increased activation of the immune system, what keeps the activated cells from attacking normal tissue as well? I could very easily see an induced autoimmune disorder stemming from a treatment like this. Additionally, how effectively are doctors able to deliver the antibodies themselves to a specific region of the body, and make sure they stay there? These questions, and more, will hopefully be answered as research is developed and advanced in the coming years.