Grant: Operating Grant: TRANSCAN-3

Our research focuses on a condition often see in older patients that is called clonal hematopoiesis of indeterminate potential (CHIP)". In CHIP, specific genetic mutations in blood-forming stem cells occur and lead to the abnormal outgrowth of certain types of blood cells. While CHIP itself does not directly cause blood cancer, it can create a persistent state of inflammation in the body. This inflammatory environment is thought to play a critical role in the development and progression of solid tumors, for instance a subtype of lung cancer and pancreatic cancer, which are both hard to treat. The mutations that occur in the blood cells of patients with particularly affect genes like TET2 and JAK2, which are responsible for the excessive release inflammatory signals. These signals include molecules called "cytokines" like IL-6 and TNF-alpha, which are known to promote inflammation and cancer growth and the spread of cancer cells. Furthermore, the altered immune cells in patients that have CHIP may weaken the body's natural ability to fight tumours, making the novel cancer treatments like immunotherapy less effective. In the project proposed here we have brought experts from different countries together to better understand the role of CHIP in cancer. We will use mouse models and patient samples to investigate how CHIP-related immune changes contribute to tumor growth and resistance to therapy. We plan to test drugs including inhibitors of specific enzymes such as LSD1 and JAK2 that are linked to CHIP to see if they can improve outcomes for patients with NSCLC and pancreatic cancer. We expect that our research will not only clarify the link between CHIP and cancer but also pave the way for new, more effective treatment strategies. Ultimately, this could improve survival and quality of life for cancer patients with CHIP, especially those with tumors that are very difficult to treat as for instance lung cancer and pancreatic cancer.