Improvement of
cancer treatment is a major challenge of medical research. Despite the immense efforts made in the improvement of diagnosis and treatment,
cancer remains a major concern and cause of morbidity and mortality. Most of the modern anti-neoplastic
therapies have severe side effects, and
tumor cells often develop drug resistance. There is promise in the new generation of treatments (gene therapy,
immunotherapy,
vaccines, etc.) that are under development, but the efficacies and side effects of such
therapies have so far been disappointing. Receptor-based
therapies are not new, but many normal cells also present the same receptors reducing the specificity of such approaches. Several lytic
peptides have been investigated because of they appear to kill
cancer cells due to changes of their membrane potential. Thus, linking receptor-specific
ligands to lytic
peptides is expected to augment the specificity of targeting and decrease the toxicity of lytic
peptides on normal cells. One such
polypeptide is hecate (an analogue to the
bee venom main component,
melittin) that preferentially kills
cancer cells at low doses. When this
peptide is fused with the 81-95
amino acid fragment of
chorionic gonadotropin-beta (CGbeta) subunit (
hecate-CGbeta), it targets cells expressing
luteinizing hormone receptor (LHR), even at very low doses, or when LHR is expressed at low level. Our recent data showed that this
peptide conjugate is efficient in destroying LHR-positive cells in xenografts and more importantly in transgenic mouse models developing LHR-positive somatic cell
tumors in gonads. The mechanism of action of
hecate-CGbeta after binding to LHR is destruction of cell membranes resulting in rapid cell death by
necrosis with minimal side effects. This review summarizes our findings on the action of this novel
peptide and considers the future potential of this family of targeting
peptides in the treatment of
neoplasias.