The Combined Therapeutical Effect of Metal-based Drugs and Radiation Therapy: The Present Status of Research

Conventional chemotherapy and radiation treatment are two cornerstones of cancer treatment but efforts are required to improve their "therapeutic window". The development of metal complexes, including platinum, has had an enormous impact on current cancer chemotherapy. However, these chemotherapeutic drugs can be employed only in the management of a limited number of cancers and, furthermore, their use causes significant side effects. Research over the past 10 years has produced new complexes containing heavy atoms other than platinum, such as iron, cobalt, or gold, which have been used in phase I and phase II trials. Recent preclinical research has shown promising results also using titanium, ruthenium, copper and silver. The anticancer activity of metal-based compounds and nanoparticles (gold and gadolinium in particular) is presently under evaluation in several laboratories in combination with or without X-ray therapy. In fact, if present in sufficiently high concentrations in the tumors, metals can act as a radiotherapy adjuvant: they possess an increased capability to absorb the X-ray radiation with respect to the water-based tissues. Low energy electrons will be then released close to the metal and, therefore, determine a local dose enhancement. This review will focus on the anticancer properties of new drugs and on the rationale for testing their usefulness in combined treatment.