Targeting Draxin in Cancer – DRAXCAN

Over the last past years, the key roles of embryonic molecules/pathways in tumorigenesis have emerged and candidate drugs targeting these molecules/pathways have been developed. This has led to the clinical assessment developmental drugs/biologics and sometimes to clinical benefit for patients as targeting Sonic Hedgehog pathway in basocellular carcinoma. The current view is that the multistep program of tumorigenesis includes the reactivation of developmental processes like EMT, migration or apoptosis resistance. Several of these developmental proteins are axonal navigation cues. More specifically, the Mehlen group (P1) has previously demonstrated that the prototypical axonal guidance netrin-1 is up-regulated in a large fraction of human cancer as a mechanism supporting cancer cell survival. NETRIS Pharma (P2) has thus developed a monoclonal antibody (mAb) blocking netrin-1/receptors interaction which is now clinically assessed in a large phase II trial. Of interest preliminary data obtained by Partner 1 support the view that another netrin-1 related guidance cue named Draxin, is also up-regulated in a large set of cancers including Glioblastoma and, similarly to netrin-1, supports cancer cell survival. Together these preliminary data and the complimentary expertise of the academic and the private partners support the development of a therapeutic approach targeting Draxin in cancer. The DRAXCAN project will thus validate the Draxin target in cancer and preclinically develop a therapeutic anti-Draxin mAb. Target validation will include (i) the pan-cancer analysis of Draxin in human cancer using both public database and materials from in-house biobanks, (ii) analysis of Draxin silencing/interference in tumor cell models but also animal tumor models. The anti-Draxin mAb development will include (i) the generation of a series of blocking Draxin mAb, (ii) the selection of a candidate Draxin mAb showing tumor growth inhibition in mice models and (iii) its humanization.