VO At the University of Kentucky, Assistant Professor of Chemistry Phoebe Glazer is looking for something more effective at killing cancer cells and less toxic to healthy cells than cisplatin. A platinumbased drug, cisplatin is one of the most commonly used cancer drugs, but leads to nausea and nerve damage. Phoebe Glazer Cisplatin essentially does a lot of damage in rapidly proliferating cells. So that’s why it’s good as a cancer drug, and it will work on a variety of different types of cancers. The problem isit will kill all types of cells. There’s this really.
Narrow window between a therapeutic dose where you’re effectively killing the cancer, and the toxic dose where you’re essentially killing the patient. That’s why I was motivated to start this project. VO Glazer’s lab team has an alternative, a drug based on ruthenium. Phoebe Glazer Ruthenium is another transition metal. It’s in the middle of the Periodic Table, and its right underneath iron. Unfortunately, like platinum, it’s a precious metal, so it’s not cheap. The reason people really like ruthenium is because you can make complexes out of it that are useful in a wide variety of applications.
You can keep the metal center, the ruthenium, the same, and put different organic ligands around it. So if you want to make a sophisticated looking moleculea complex moleculeyou can swap out the different organic pieces and build in three dimensions molecules that will look different and potentially have different functions and behavior. That’s why we think it’s a good scaffold that you can use to build a drug. VO Postdoc Matthew Dickerson explains how these rutheniumbased drugs would kill tumors. MATTHEW DICKERSON What I’m trying to do is I’m trying to take the molecules, put them.
LightActivated Cancer Drugs at UK
Into nanoparticles to prolong the circulation time in the body, as well as hopefully deliver them to the tumor more effectively. One of the major limiting factors in traditional chemotherapy is the fact that it’s nontargeted. You basically inject it into the patient, and it goes where it will. What we want to do is target the chemotherapeutics directly to the tumor. We can inject those into the patient, and then when we hit the patient with lightlocally to the tumoronly the compounds actually in the tumor activated so that they become toxic.
VO Using light from a fiberoptic probe, Glazer’s ruthenium molecules would be switched on, and cause DNA damage only to the cancerous tumor. DAVID HEIDARY We’re also trying to uncover how these molecules work. How do they attack the cell in such a way that it causes them to die in the presence of light So we’re investigating the mechanism of action for these molecules. YANG SUN This is the most exciting part of the project because we’ve found that some of the compounds kill cells by targeting DNA and damaging DNA.
Phoebe Glazer If you can create a molecule that in its intact form is inactive, but when you shine light on it, you create a DNA damaging component and then another component that would have a totally different activity. Then you have the chance of hitting the cell twice. That’s the hypothesisthat’s the idea. One drug could have two different mechanisms. VO Glazer has shown that these ruthenium molecules are up to three times as potent as cisplatin. In January 2013, she received a fouryear grant from the American Cancer Society to develop a family of ruthenium molecules to fight different kinds of cancer.