Melvin Calvin Lecture: Understanding and Improving Platinum Anticancer Drugs

Seminar | April 16 | 11 a.m.-12 p.m. | 120 Latimer Hall

 Stephen Lippard, Department of Chemistry, MIT

 College of Chemistry

Platinum compounds are a mainstay of cancer therapy. Barnett Rosenberg’s group at Michigan State University discovered the biological action of cis-diamminedichloroplatinum(II), or cisplatin, in the late 1960’s. Our laboratory 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. Platination of the genome evokes cell death pathways and attempts at damage repair. If the former prevails the cancer can be cured; the latter neutralizes the effect of the drug. Details of these processes have been elucidated. Binding of high mobility group (HMG) proteins to cisplatin 1,2-intrastrand d(GpG) cross-links, the major DNA adducts, blocks excision repair, an event that facilitates the ability of the drug to cure testicular cancer. This information has recently been used to sensitize additional cancer cell types to cisplatin by introduction of a particular HMG protein, HMGB4, which has the potential to cure cancer in humans without regard to tissue of origin. Details will be provided. Finally, the use of Pt(IV) pro-drugs to deliver cisplatin selectively to cancer cells via the “Warburg effect” was established, and a variation was invented by Blend Therapeutics to devise a novel platinum-based cancer therapy that is nearing completion of a Phase I clinical study. This work was supported by the National Cancer Institute.

 Light refreshments will be served at 10:50 at The Coffee Lab, 510-643-0572