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Dr. Skip Burris from the Sarah Cannon Research Institute discusses targeted therapies – what are they and how do they work?

Q: Welcome to Understanding Cancer.  Today we’re visiting with Dr. Skip Burris, who is the director of drug development at the Sarah Cannon Research Institute in Nashville, Tennessee.  Dr. Burris has extensive experience in new drug development as well as clinical trials in general, with a focus on oncology.  Welcome.

A: Thank you.

Q: In recent years there’s been a little bit of a movement to try to develop drugs that are different than traditional chemotherapy drugs, drugs that we call targeted therapies.  Can you tell us a little bit about what a targeted therapy is, how it works, and what their relevance is today?

A: So targeted therapies – and I think we’ve always liked to think that our chemotherapies targeted the cancer cell – but the fact of the matter is we’re into a new generation of identifying these targets.  I think the simplest way to think about it is what we’ve known about breast cancer for years, and that’s certain breast cancer cells actually have estrogen receptors, and that we can use a hormonal treatment to block that estrogen receptor and have a benefit.

Now we know that there are many more receptors and many more growth factors that stimulate cancer cells to grow and divide, and we’re beginning to understand the pathways that can block those.  So we’re seeing individualized treatment for cancers.  We’re seeing drugs that work in a specific type of cancer as opposed to across all types of malignancies.  We’ve seen that with some oral drugs that we use to treat lung cancer with, a certain population of patients that have a mutation, and they’re very, very sensitive to these oral biologic.  They’re not chemotherapy.  They go inside the cell and turn it off, keep it from growing and dividing.

I use the analogy: it would be no different than turning off the lights with the light switch.  The problem with cancer cells is you don’t know what the light switch is for many of them.  But as we begin to identify the targets, we know what drugs we can give to these patients and actually turn that switch off and keep the cancer cells from growing and dividing.  We’ve seen these targeted drugs be oral small molecule, so oral drugs that can be given and get inside the cell.

And the other big class of targeted agents are these monoclonal antibodies.  They’re given intravenously through the vein and they’re able to go and attack the cancer cell.  And actually, now we’re starting some research and seeing some promise on actually linking chemotherapy to these antibodies so it gets just to the cancer cell and doesn’t affect some of the other normal cells in the body.

Q: And conceptually the key theoretical benefit of targeted therapy is that it exclusively attacks the cancer cell, but spares the normal cells?

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A: Exactly.  And I think that that’s all part of keeping the patient stronger, the immune system stronger, avoiding some of the side effects for therapy.  We’re learning about new side effects, we’re learning about different ways to manage those.  It’s interesting, with some of the new targeted therapies, one of the more common side effects that we’re actually seeing described is fatigue, or the patient’s energy level.

And I take that as a glass half full thing.  One is we’re not talking about nausea or we’re not talking about diarrhea, we’re not talking about hair loss, so there’s other things to complain about.  And then the other part is these patients are out there trying to be more active.  They’re not having the acute side effects, so they’re pushing themselves a little bit more, and so a lack of energy, fatigue, and a little more tired is the symptom that they’re experiencing.

Q: So because they’re, in essence, feeling better, their expectations are a little higher?

A: Yeah, when the patient comes in and they’re really whipped more than they would be usually, more fatigued than usual from mowing their grass, I mean, that’s not a bad conversation to be having.  They’re out there mowing their grass and doing their yard work and getting on with the daily activities of life.

Q: Are there any advantages to combining targeted therapies with traditional chemotherapy drugs?

A: There is.  I think that we’re seeing some real approaches with regard to designing those.  Some of the targeted therapies actually allow the chemotherapy to work better.  We’ve seen some excitement with some of these drugs that are what we call angiogenesis inhibitors.  They interfere with the natural blood vessel growth and development that cancer cells need.  So cancer cells need new blood vessels to continue to divide and try to build a new nest or a metastases.

So when we give chemotherapy with those drugs, we’re seeing better penetration of the chemotherapy into the cancer cells, and we’re seeing more tumors shrink.  There’s also the advantage of giving the targeted therapy with the chemotherapy that after the chemotherapy’s done its job, after it’s killed as many cells as it can, that the targeted cells can keep those from re-growing, and can put the finger in the dike and stop the cancer cells from returning.

Q: Well, Skip, thank you for your time today, and we really look forward to having you back.

A: Thank you.

[End of recording.]