"Understanding and Improving Platinum Anticancer Drugs"
Stephen J. Lippard, PhD
Arthur Amos Noyes Professor
Massachusetts Institute of Technology
Platinum compounds are a mainstay of cancer therapy, with more than half of all patients receiving an infusion of one of three FDA approved drugs (cisplatin, carboplatin, and oxaliplatin). The biological action of cisplatin was discovered by serendipity in the late 1960s. Our laboratory has subsequently established the chemical nature of events leading up to the binding of platinum anticancer drugs to DNA, their principal target in the nucleus of cancer cells. The major adducts are cross-links between two adjacent nucleotides on one strand of the double helix, which bend and distort the duplex, interrupting cellular processing by RNA and DNA polymerases. We discovered more recently that related platinum compounds, capable of forming only a single link to DNA, are also extremely active against cancer cells, leading to exciting new strategies and candidates for drug development. Details of how these 'monofunctional' compounds work will be described. From the chemical principles learned in the process have emerged a much larger family of anticancer drug candidates, including those based on osmium and rhenium in addition to platinum.
Stephen J. Lippard, whose research spans the fields of biological and inorganic chemistry, is the Arthur Amos Noyes Professor of Chemistry at the Massachusetts Institute of Technology.
Lippard studies biological interactions involving metal ions, focusing on reactions and physical and structural properties of metal complexes. Such complexes can be useful as cancer drugs and as models for the active sites of metalloproteins. Metal ions also promote key biological reactions in enzymes and metal complexes can be employed to sense biological signaling agents.
This is event is jointly sponsored by the Integrated Cancer Research Center and Georgia Tech's School of Chemistry and Biochemistry.