Engineering Intracellular Iron Sequestration to Target Cancer Growth

This talk will focus on molecular design strategies currently pursued in the Tomat laboratory to target the central role of iron in cancer growth. Iron supports enhanced proliferation and survival of malignant cells as well as remodeling of the tumor microenvironment to facilitate motility and metastatic behavior. Several iron chelators have shown promising results in clinical trials for cancer indications; however, no iron-sequestering compound is currently approved for cancer treatment. To increase the selectivity and efficacy of iron-binding approaches, we are exploring strategies to release chelators only after cellular uptake. Reductive activation switches are particularly advantageous owing to the more reducing conditions found in malignant cells when compared to neighboring normal cells. Overall, the molecular engineering of prochelators is expected to improve the ability of iron-sequestration approaches to contrast cancer growth while minimizing unwanted side effects.