ROBO2 as a tumor suppressor in pancreas and lung: biology and actionability for therapy

Within ~ 15 years, pancreatic cancer is predicted to become the 2nd deadliest cancer in the world, after lung cancer. Current therapies have failed to lead to significant therapeutic improvements in the majority of lung and pancreatic cancer patients. We propose a study on a gene (ROBO2) which its loss is estimated to occur in the majority of lung and pancreatic cancers and is significantly associated with poor overall survival. According to our data and literature, loss of ROBO2 leads to activation of pro-cancer pathways and also makes the microenvironment fertile for cancer-associated events such as activation of neighboring stromal cells and induction of immune-suppressive markers. Despite that existing drugs could counteract these effects, we are not aware of any comprehensive
study that has addressed this. Besides that, there is a heterogeneous expression of other partners and ligands of ROBO2 in the tumor, complicating the landscape. We hypothesize that targeting ROBO2- related pathways can impair cancer progression. We aim to study the biology of ROBO2 loss in cancer comprehensively, in different scenarios of partner and ligand expression and, not solely in tumor cells but also in the presence of tumor-microenvironment
components. Ultimately, we determine the drugability in these scenarios using state of the art experimental techniques and consulting public databases. This project can provide significant benefits for a large fraction of cancer patients