L1-CAM as a target for treatment of cancer with monoclonal antibodies.

Abstract

L1 cell adhesion molecule (L1-CAM) is a neuronal adhesion molecule which is expressed in many tumor entities. L1-CAM was shown to be involved in proliferation, invasion and metastasis both in vitro and in vivo. L1-CAM is engaged in homophilic interactions and complexes with many other ligands in a context-dependent manner. Activation and modulation of the extracellular signal-related kinase pathway by L1-CAM has been documented. In normal tissues, L1-CAM expression is restricted to nerve bundles and kidney tubules; however, L1-CAM is expressed in many tumor entities and, with the exception of neuroblastoma, L1-CAM expression correlates with poor prognosis. L1-CAM occurs in two isoforms, full-length L1-CAM and a variant in which exons 2 and 27 have been deleted. Preclinical experiments with available monoclonal antibodies are summarized and L1-CAM is analysed as a target for treatment of cancer with monoclonal antibodies.