Dissecting and targeting malignant cell-fibroblast crosstalk driving cachexia in pancreatic cancer

ongoing

"Cancer-associated “cachexia” is a debilitating condition that causes patients to lose weight and muscle, which limits treatment options and worsens survival. Often patients diagnosed with pancreatic cancer, a lethal and increasingly common malignancy, are affected by cachexia. Little is known about cachexia and no therapies exist. It is thus important to identify causes of cachexia to develop treatments. Pancreatic tumours contain abundant non-cancerous cells, called ""fibroblasts"", that promote cancer progression. My host laboratory found various types of fibroblasts that promote pancreatic cancer in different ways. Moreover, they found that genetic mutations of the cancer cells change the fibroblasts. While lots is known about how fibroblasts promote cancer, we know little about how they affect cachexia. My research objective aims to identify features of pancreatic cancer fibroblasts that promote cachexia to guide the development of therapies. I first aim to determine how genetic mutations that alter the composition of pancreatic cancer fibroblasts affect cachexia (Objective 1). I will then test how pancreatic cancer-associated cachexia is affected when fibroblast composition is altered using mouse models that were recently engineered by my host laboratory (Objective 2). This work will highlight candidate therapeutic targets of cachexia. Importantly, cachexia also affects patients with other cancers and diseases, and fibroblasts in these conditions share features with pancreatic cancer fibroblasts. Thus, my project could have a broad impact. My research background in pancreatic cancer and the models of the host laboratory will guarantee the successful completion of this project. Working with the host supervisor, a world-leading expert on pancreatic cancer fibroblasts, along with the training program outlined, will have a long-lasting impact on my scientific career and will help me transition into an independent position as a cachexia-focused researcher."