An impromptu conversation leads to innovative research in small cell lung cancer

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Juhi Kunde, MA

LUNGevity awardee Dr. Julien Sage of Stanford University and I recently discussed how a simple conversation at a networking event about small cell lung cancer (SCLC) paved the way for innovative research that has the potential to improve survival rates for patients.

Currently, there is a lot of research being conducted to try to use the body’s natural defenses—the immune system—to eradicate disease. This field, called immunotherapy, is growing quickly and providing promising results in many types of cancer. Unfortunately, SCLC continues to have low survival rates. Dr. Sage and his team of collaborators received a 2014 LUNGevity Targeted Therapeutics Award to develop immunotherapy techniques that target small cell. Dr. Sage spoke about this cutting-edge research and the LUNGevity funding that made his work possible.

LUNGevity: How did you get the idea for this project?

Julien Sage: I have been interested in small cell for about 15 years. My postdoctoral research involved SCLC, and I have continued to study the disease in my own lab at Stanford University. A couple of years ago, I attended a networking retreat for MD/PhD students and their mentors, where I had the opportunity to brainstorm and discuss new research ideas with scientists from other laboratories. That was where I started discussions with Kipp Weiskopf, a student in Dr. Irving Weissman’s lab. Dr. Weissman is a world-class researcher with a long list of honors and awards; currently, he is the director of the Institute of Stem Cell Biology and Regenerative Medicine at Stanford. He and his lab members knew a lot about cancer immunology and I knew a lot about small cell, so together we hoped to make a powerful team.

L: How did the LUNGevity funding enable you to conduct this research?

JS: Our two labs did a bit of preliminary work together but this was a new area of focus for both labs, so we needed funding to get the project under way. We were grateful to receive the LUNGevity award. It gave us two years of funding to do innovative research. We gathered important data that were recently published, and that research allowed us to recently apply for a large federal grant to continue working on improving treatments for patients with SCLC.

L: What was the focus of your work?

JS: Our immune systems have healthy “vacuum cleaner” cells, called macrophages, which go around eating up bacteria, dead cells, and other things that could make us sick. Most healthy cells in our bodies have “do not eat me” flags, called CD47, that signal macrophages to leave them alone. Every SCLC tumor cell that we tested also had this flag on its surface; it is one of the ways the tumor evades the body’s natural defenses. We wanted to know what would happen if we blocked the CD47 signal on SCLC tumor cells. We hoped that maybe the macrophages would start eating the tumor cells. And that is what happened. We were able to turn these immune system cells into cancer-fighting machines. 

L: What are the next steps?

JS: Our labs want to combine this technique with other therapeutic approaches. For example, we want to know what happens when we combine chemotherapy with an agent that blocks the CD47 “do not eat me” signal on SCLC tumors. Chemotherapy kills cells, which leads to the accumulation of cellular debris and further activates the “vacuum cleaner” macrophages. We hope that by blocking CD47, we can enlist the macrophages in our cancer fight and enhance the overall effects of chemotherapy. In addition, we are looking for other flags on the surface of SCLC cells that might be good ways to identify or specifically target SCLC cells, with our ultimate goal being the development of drugs that will increase survival rates for SCLC patients.

Juhi Kunde, MA, is a science writer for LUNGevity.

Small cell lung cancer
Targeted therapy

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