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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 platinum-based 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 is--it 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 molecule--a complex molecule--you
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 ruthenium-based drugs would kill tumors.
MATTHEW DICKERSON: What I'm trying to do is I'm trying to take the molecules, put them
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 non-targeted.
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 light--locally to the tumor--only
the compounds actually in the tumor activated so that they become toxic.
VO: Using light from a fiber-optic 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 hypothesis--that'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 four-year grant from the American Cancer
Society to develop a family of ruthenium molecules to fight different kinds of cancer.
Phoebe Glazer: Taking it from essentially some initial molecules that prove that the
concept works to the point where we might actually have molecules that have a chance
of helping someone.
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