Abstract: In netrin-1 expressing tumor cells, netrin-1 interference triggers Mcl-1 degradation, restricted to these netrin-1 expressing tumor cells. It is proposed a netrin-1 interference to trigger tumor-specific Mcl-1 degradation. In addition, netrin-1 interference may be combined with BH3-mimetics, especially a Bcl-2 inhibitor. Netrin-1 interference is made using anti-netrin-1 antibodies. The invention proposes an anti-netrin-1 antibody for use as a tumor-specific Mcl-1 inhibitor in the treatment of a Mcl-1+ tumor, more particularly a Mcl-1+, netrin-1+ and netrin-1 receptor+, especially UNC5B+, tumor. Also provided is a combination of an anti-netrin-1 antibody and a Bcl-2 inhibitor, such as Venetoclax.

Abstract: The present disclosure is directed to the combination or combined use of (i) a compound able to disrupt or impede netrin-1/netrin-1 receptors interaction or netrin-1-mediated receptor dimerization, also called herein a NTN1 neutralizing agent, which compound may be an antibody binding to netrin-1 or anti-netrin-1 antibody, and (ii) an immune checkpoint inhibitor, in the treatment of cancer. The composition may comprise an anti-netrin-1 antibody and an immune checkpoint inhibitor, for use as an anticancerous drug with a simultaneous, separate or sequential administration of the anti-netrin-1 antibody and the immune checkpoint inhibitor to a patient.

Abstract: The invention is the combination or combined use of (i) a compound able to disrupt or impede netrin-1/netrin-1 receptors interaction or netrin-1-mediated receptor dimerization, also called herein a NTN1 neutralizing agent, which compound may be an antibody binding to netrin-1 or anti-netrin-1 antibody, and (ii) an immune checkpoint inhibitor, in the treatment of cancer. The composition may comprise an anti-netrin-1 antibody and an immune checkpoint inhibitor, for use as an anticancerous drug with a simultaneous, separate or sequential administration of the anti-netrin-1 antibody and the immune checkpoint inhibitor to a patient.

Abstract: The present invention is based on the finding that Netrin-(1) is retained in a stickier manner in the cell matrix at the cell periphery of the cancer cells, whereas Netrin-(1) is expressed in adults specifically in some tumors. It is also shown herein that Netrin-(1) is expressed very early during tumor formation. This makes Netrin-(1) an unexpected very specific target for imagery and/or targeted therapy. The present invention thus relates to compounds comprising an anti-Netrin-1 antibody, especially NP(137), a chelating moiety, optionally associated with a radioisotope, and their use either in imagery, diagnosis, especially companion diagnosis, or in targeted therapy. New diagnostic tests, which may be companion tests, and new cancer therapies, that may be combined to the companion test, are also proposed.

Abstract: The netrin-1 protein displays anti-inflammatory activity in the liver and is an unexpected proinflammatory factor in CLD. The present invention provides for blocking or capturing netrin-1 in the liver for treating liver inflammation, and thus methods for treating liver inflammation. To perform this, the invention makes use of a polyclonal or monoclonal antibody specifically binding to netrin-1, including a series of humanized monoclonal antibodies.

Abstract: The subject matter of the present invention relates to an in vitro method for the screening of anti-cancer compounds based on the capacity for these compound to interact with netrin-1 receptor and/or to inhibit the dimerization of the intracellular domain of the netrin-1 receptor expressed in tumor cells. The invention also relates to a method for predicting the presence of metastatic or aggressive cancer, or for determining the efficiency of an anti-cancer treatment based on the measuring of the expression level of netrin-1. The invention further comprises kits and compounds as a medicament for the treatment of cancer such as metastatic breast cancer, related to the overexpression of netrin-1 by the tumor cells.

Abstract: The invention is the combination or combined use of (i) a compound able to disrupt or impede netrin-1/netrin-1 receptors interaction or netrin-1-mediated receptor dimerization, also called herein a NTN1 neutralizing agent, which compound may be an antibody binding to netrin-1 or anti-netrin-1 antibody, and (ii) an immune checkpoint inhibitor, in the treatment of cancer. The composition may comprise an anti-netrin-1 antibody and an immune checkpoint inhibitor, for use as an anticancerous drug with a simultaneous, separate or sequential administration of the anti-netrin-1 antibody and the immune checkpoint inhibitor to a patient.

Abstract: The subject matter of the present invention relates to an in vitro method for the screening of anti-cancer compounds based on the capacity for these compound to interact with netrin-1 receptor and/or to inhibit the dimerization of the intracellular domain of the netrin-1 receptor expressed in tumor cells. The invention also relates to a method for predicting the presence of metastatic or aggressive cancer, or for determining the efficiency of an anti-cancer treatment based on the measuring of the expression level of netrin-1. The invention further comprises kits and compounds as a medicament for the treatment of cancer such as metastatic breast cancer, related to the overexpression of netrin-1 by the tumor cells.

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 invention relates to a method for producing induced pluripotent stem cells (iPS) by culturing somatic cells subjected to a cellular reprogramming method, characterised in that the somatic cells are cultured in the presence of netrin-1 or an analogue of netrin-1 at least at the beginning of the cellular reprogramming method.

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 subject matter of the present invention relates to an in vitro method for the screening of anti-cancer compounds based on the capacity for these compound to interact with netrin-1 receptor and/or to inhibit the dimerization of the intracellular domain of the netrin-1 receptor expressed in tumor cells. The invention also relates to a method for predicting the presence of metastatic or aggressive cancer, or for determining the efficiency of an anti-cancer treatment based on the measuring of the expression level of netrin-1. The invention further comprises kits and compounds as a medicament for the treatment of cancer such as metastatic breast cancer, related to the overexpression of netrin-1 by the tumor cells.

Abstract: The present invention relates to DCC-fusion proteins, nucleic acid molecules encoding the DCC-fusion proteins, as well as methods for their production and their use in treatment of cancer such as colorectal cancer, NSCLC and metastatic breast cancer. The present invention also relates to methods of treating cancer such as colorectal cancer, NSCLC and metastatic breast cancer by administering DCC-fusion proteins.

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.

Abstract: The invention provides methods and compositions for reducing or inhibiting net beta-amyloid peptide production and/or amyloid plaque formation. The methods and compositions involve administering a netrin-1 polypeptide or netrin-1 therapeutic to a subject in need thereof.

Abstract: The present invention relates to an in vitro method for selecting a compound capable to induce the death of endothelial cells, preferably endothelial cells from vessels or neovessels. The invention further comprises the use of netrin-1 function inhibitors as compounds capable to induce the death of endothelial cells, preferably endothelial cells from vessels or neovessels of tumor expressing netrin-1. Finally, the invention relates to a kit for the selection of a compound capable to induce the death of endothelial cells.

Abstract: The subject matter of the present invention relates to an in vitro method for the screening of anti-cancer compounds based on the capacity for these compound to interact with netrin-1 receptor and/or to inhibit the dimerization of the intracellular domain of the netrin-1 receptor expressed in tumor cells. The invention also relates to a method for predicting the presence of metastatic or aggressive cancer, or for determining the efficiency of an anti-cancer treatment based on the measuring of the expression level of netrin-1. The invention further comprises kits and compounds as a medicament for the treatment of cancer such as metastatic breast cancer, related to the overexpression of netrin-1 by the tumor cells.

Abstract: The invention provides a method for reducing or inhibiting net beta-amyloid peptide production and amyloid plaque formation associated with Alzheimer's Disease by administering to a subject an amount of a netrin-1 polypeptide, wherein the netrin-1 polypeptide comprises an amino acid sequence that a) binds to a naturally occurring APP protein and b) inhibits A? peptide production. A netrin-1 polypeptide has an amino acid sequence sufficient for specific binding of the netrin-1 polypeptide to the APP protein. A netrin-1 polypeptide can mimic netrin-1-mediated signal transduction by altering the localization, protein-protein binding and/or enzymatic activity of an intracellular protein involved in an APP signal pathway.