Stephen J. Lippard
Lecture: Understanding and Improving Platinum Anticancer Drugs
Tuesday, April 1, 2014
4 pm, MIT Room 10-250
Stephen Lippard, the Arthur Amos Noyes professor in the Department of Chemistry, is MIT’s James R. Killian Jr. Faculty Achievement Award winner for 2013–2014.
Professor Lippard has spent his career studying the role of inorganic molecules, especially metal ions and their complexes, in critical processes of biological systems. He has made pioneering contributions in understanding the mechanism of the cancer drug cisplatin and in designing new variants to combat drug resistance and side effects.
Understanding and Improving Platinum Anticancer Drugs
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 serendipitously in the late 1960s. Our laboratory has subsequently established the chemical structures of the major adducts formed upon the binding of platinum anticancer drugs to DNA, their principal target in the nucleus of cancer cells. These adducts are cross-links between two adjacent nucleotides on one strand of the double helix. These cross-links 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 with much less distortion, are also extremely active against cancer cells, leading to exciting new strategies and candidates for drug development. Details of how these ‘monofunctional’ compounds as well as the three approved drugs 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 other third row transition metals, in addition to platinum.
Read more at MIT News.