Kipp Weiskopf, MD, PhD

“Targeted therapies” are drugs that turn off molecular switches in cancer cells to stop their growth. These therapies allow many lung cancer patients to live longer, but they do not cure patients. In most cases, the cancer returns or continues to grow after a few years. Immunotherapies, which train a patient’s immune system to fight cancer, have emerged as another promising treatment for lung cancer. Although there has been remarkable success using immunotherapies, these drugs also do not cure the majority of lung cancer patients. We will investigate how therapies that activate immune cells called macrophages can be used to enhance targeted therapies for cancer. We will focus our effort on lung cancers with specific mutations in a gene called KRAS, but we expect our findings will apply to other types of lung cancer as well. We hope that by combining these two types of therapies, we will identify a strategy to cure certain types of lung cancer.

Update:
We have found that immune cells called macrophages can be stimulated to attack KRAS mutant lung cancer cells. Furthermore, we have identified a novel combination of drugs that make KRAS mutant lung cancer cells more vulnerable to being attacked by macrophages. Our study indicates this combination therapy could benefit patients with KRAS mutant lung cancer. We hope these concepts will be tested in clinical trials as a next step.

Final Project Update: 
Our research focuses on the interaction between the immune system and lung cancer. Specifically, we investigated how macrophages, cells of the innate immune system, interact with lung cancer cells containing a KRAS mutation. Macrophages are large immune cells that have the ability to attack and eliminate cancer cells by engulfing and destroying them via a process known as phagocytosis. We found that new targeted therapies that block growth signals in KRAS mutant lung cancer cells make these cancer cells more vulnerable to macrophage attack. We have also discovered new genes and signaling pathways that KRAS mutant lung cancer cells use to evade detection by macrophages. Our research identified new drug combinations for KRAS mutant lung cancer, and the therapeutic strategies we discovered warrant further investigation in clinical trials as a next step to translate our discoveries. We have also identified receptors on the surface of KRAS mutant lung cancer cells that could be good targets for the development of new therapies in the future. Overall, the Catalyst Award has been invaluable for our lab. It has helped us advance our research project, secure additional sources of funding, and broaden the scope of our work to other types of lung cancer.