Cancer Science and Therapy

Cancer treatment experienced significant advance over the last years. This has been mainly due to therapy targeting of key biological mechanisms such as cell survival, proliferation, apoptosis, angiogenesis and, more recently, tumor immune response. Cell communication, however, despite playing a fundamental role in all steps of tumor progression, up to metastasis and therapy resistance, is still off the cancer therapy landscape. Hence, the major challenge of our work is to bring cell communication into the realm of cancer therapy. Exosomes, extracellular vesicles secreted by all cells, are key mediators of cell to-cell communication in cancer. We have identified a network of communication mediated by cancer exosomes in vivo, through the identification of their recipient cells. Additionally we show that targeting the most frequent pancreatic cancer exosomes communication route can be an effective target for pancreatic cancer therapy. Our strategy includes unique genetically engineered mouse models (GEMMs), which allow for the first time to trace exosomes in vivo and model therapeutic targeting of exosomes biogenesis. Our work demonstrates the in vivo significance of pancreatic cancer exosomes and opens a new avenue for groundbreaking discoveries in the treatment of pancreatic cancer and, eventually, other cancers.