Anti-galectin compounds as potential anti-cancer drugs

Abstract

Galectins form a family of carbohydrate-binding proteins defined by their affinity for beta-galactosides containing glycoconjugates. The carbohydrate recognition domain (CRD) is responsible for the specificity of galectins for saccharides. This binding may result in modulated cell proliferation, cell death and cell migration, three processes that are intimately involved in cancer initiation and progression. Galectins can also display protein-protein types of interactions with their binding partners. Certain galectins directly involved in cancer progression seem to be promising targets for the development of novel therapeutic strategies to combat cancer. Indeed, migrating cancer cells resistant to apoptosis still constitute the principal target for the cytotoxic drugs used to treat cancer patients. Reducing the levels of migration in apoptosis-resistant cancer cells can restore certain levels of sensitivity to apoptosis (and so to pro-apoptotic drugs) in restricted-migration cancer cells. Anti-galectin agents can restrict the levels of migration of several types of cancer cell and should therefore be used in association with cytotoxic drugs to combat metastatic cancer. We provide experimental proof in support of this concept. While the present review focuses on various experimental strategies to impair cancer progression by targeting certain types of galectins, it pays particular attention to glioblastomas, which constitute the ultimate level of malignancy in primary brain tumors. Glioblastomas form the most common type of malignant brain tumor in children and adults, and no glioblastoma patient has been cured to date.