Abstract: The application discloses method of treatment of cancer utilizing a linear or substantially linear epitope on netrin-1 that likely corresponds to the specific binding region of netrin-1 to receptor, in particular of the UNC5 class, especially UNC5B and UNC5A, or alternatively corresponds to a region nearby the specific binding region of netrin-1 to receptor that when bound to an antibody prevents netrin-1/receptor interaction. This determination of a linear epitope allows for the production of antibodies binding to netrin-1 and interfering with netrin-1/receptor interaction, thereby inducing apoptosis or cell death of tumour cells expressing or overexpressing netrin-1 and at least one netrin-1 receptor, owing the fact that this interaction inhibits netrin-1 binding to a receptor and the multimerization of the receptor. The application also discloses a murine monoclonal antibody directed against this epitope and various humanized forms thereof.

Abstract: The application discloses a linear or substantially linear epitope on netrin-1 that likely corresponds to the specific binding region of netrin-1 to receptor, in particular of the UNC5 class, especially UNC5B and UNC5A, or alternatively corresponds to a region nearby the specific binding region of netrin-1 to receptor that when bound to an antibody prevents netrin-1/receptor interaction. This determination of a linear epitope allows the Applicant to produce antibodies binding to netrin-1 and interfering with netrin-1/receptor interaction, thereby inducing apoptosis or cell death of tumour cells expressing or overexpressing netrin-1 and at least one netrin-1 receptor, owing the fact that this interaction inhibits netrin-1 binding to a receptor and the multimerization of the receptor. The application discloses a murine monoclonal antibody directed against this epitope and various humanized forms thereof.

Abstract: Pharmaceutical composition comprising a chemotherapeutic drug and a netrin-1 interfering drug or a vector capable of expressing a netrin-1 interfering drug in vivo, in a pharmaceutically acceptable carrier or vehicle. The chemotherapeutic drug is selected from those able to induce over expression of netrin-1 in cancer cells. The combination is associated with synergic anti-cancer effect.

Abstract: The present invention is related to the treatment of certain cancers using antagonists of the binding between a Plexin and a Sema3E. The invention may be helpful in treating primary cancer cell development and metastasis development wherein Sema3E is expressed, in particular overexpressed by the tumoral cells or the stroma. Breast cancer, in particular with distant metastases is concerned. Prostate cancer, melanoma and glioblastoma are also concerned. The antagonist may be any molecule that specifically binds to PlexinD1 or Sema3E and blocks the Sema3E/PlexinD1 binding. In an embodiment, the antagonist is a polypeptide or an antibody.

Abstract: A method for inducing apoptosis of tumoral cells in a patient having cancer cells bearing Cell-adhesion molecule-related/Downregulated by Oncogenes (CDO) receptors and expressing Sonic Hedgehog (SHH), including administering to the patient an effective amount of an agonist of CDO's apoptotic function, wherein the agonist is selected from the group consisting of a CDO fragment, a fusion protein comprising a CDO fragment, an antibody against SHH, and an siRNA which is capable of inhibiting SHH expression, and related CDO fragments, fusion proteins comprising a CDO fragment, antibodies against SHH, and siRNAs which are capable of inhibiting SHH expression.