A method of treating cancer in a subject includes administering to the subject a therapeutically effective amount of an agent that specifically binds to or complexes with a proteolytically cleaved extracellular fragment of an immunoglobulin (Ig) superfamily cell adhesion molecule (CAM) or its receptor that is expressed by a cancer cell or another cell in the cancer cell microenvironment. The agent inhibits the cell adhesion function of the cleaved extracellular fragment or its receptor.