**Josh's Journey: What is Cancer?**

*Drum Beats Play*

**Josh:** Hey. My name is Josh Oppenheimer and today I am on a quest to
find the answers to life's most challenging question. No, it's not who's
going to win American Idol or how many licks it takes to get to the
center of a tootsie pop, but What is Cancer? If you're ready, then
follow me as I criss-cross the NIH campus in Bethesda, Maryland to find
the answer. Before we begin, let me tell you a little about myself. I am
a high school student who is very interested in science, and has taken
up an internship at NIH for the summer. I am working in the Center for
Cancer Research at the National Cancer Institute. But enough about me,
we gotta find the answer to what is cancer. Now get ready, 'cause here
we goooo!

*Drum Beats Play*

> Let's begin our search by figuring out some background information
> about cancer, and I'm going straight to the top. Dr. John Niederhuber,
> who is the Director of the National Cancer Institute, a presidential
> appointed position, seems like the perfect person. *Knock. Knock.*
> Hello Dr. Niederhuber. Thanks so much for talking with us. Let' get
> right into it. Let's start of with a little about how you became the
> director. What got you into science and then specifically cancer
> related research?

**Niederhuber:** In medical school, I was always very interested in the
science behind medical problems, and during the later part of my medical
school, I was able to work in a research laboratory between my junior
and senior year of medical school. And again, that was further
confirmation that I really liked science, as well as clinical medicine.
I wanted to try to develop a career that would take me down the route of
being a professor of medicine, where I could have both laboratory work
and patient contact, and where I could do teaching.

**Josh:** The NCI is a big place that spends a lot of money on research,
almost \$5 billion a year. Where does all that money go?

**Niederhuber:** A good portion of the \$5 billion, \$4.8 billion to be
exact, comes in and is already committed to support scientists,
researchers outside the NCI. They are at major university research
laboratories across the country. About 82% of our budget goes for
funding of our extramural scientists. They are scientists based at our
universities and colleges across the country.

**Josh:** As a surgeon, when a patient asks you what cancer is and why
it is so deadly, how do you respond?

**Niederhuber:** I usually start off by telling them how cancer is
something we still don't know a lot about in terms of how its starts,
how it progresses and how it spreads throughout the body. That our goal
is always to try to find it and diagnose it as early as we can, because
the earlier we can diagnose it, the more chance we have of curing it or
not having it come back. So basically, cancer is an abnormal growth of
normal cells.

**Josh:** What do you wish more people understood about cancer?

**Niederhuber:** I'm always struck by a good friend of mine, a lung
cancer specialist. He was once asked the question, how many cigarettes
can I smoke before it's a serious risk, and he immediately responded by
saying, one. I want especially your audience to know that it is
important to be smart, important to make good, sound decisions about
your life and how you live your life, in terms of exercise, diet, weight
control, not using cigarettes, tobacco products, drugs, alcohol, things
like that. All of those things will certainly be negative factors in
your having a healthy lifestyle, not just cancer, but other diseases, as
well.

**Josh:** What advice can you give students who are thinking about a
career in cancer research?

**Niederhuber:** Study hard, work hard. Those of you who live in this
area should take advantage of the many programs at the NIH. I've
recently had a student in my own laboratory, and she spent the summer
with me before she went to begin her year at Harvard, and she's back
again this summer to spend another summer with me in my laboratory. I
think you have tremendous opportunities -- I worry a lot, and I've said
this many times, and I again stress my concern that for reasons I don't
quite clearly understand, are young people don't seem as interested or
as excited about science. And I worry about our country losing our
status internationally in terms of science, and I'm hoping that we can
do things at the NCI and at the National Institutes of Health that will
tell the story of all the opportunities and excitement in ways that if
you hear them while in high school, you will be as excited as I am, and
that you will want to explore the possibility of entering some aspect of
this field. There are many, many things you can do with a background in
medicine, or a background in medicine and science. There are all kinds
of career opportunities, very exciting career opportunities for you. So
I'd encourage you to do that.

**Josh:** And finally, do you see any exciting frontiers in cancer
research?

**Niederhuber:** Well, we're very excited by the work we are doing,
understanding the genetic basis of cancer, so we're doing a lot of work,
investing a lot of resources, to look at what we call your germline
genes, the DNA that you bring into life. And we're looking at that very
carefully to identify the sites or regions that predict that you would
have an increase risk, not just for cancer, but for other diseases,
chronic diseases, as well, arthritis, diabetes, so forth, even HIV. I'm
very excited about the work we are doing. First as a pilot study,
patients with breast cancer, ovarian cancer, or lung cancer, and we're
sequencing the genes in those tumors.

**Josh:** Wow. Thanks so much! I think we're now ready to explore the
campus and get into the specifics about cancer. Thanks again Dr.
Niederhuber.

*Drum Beats*

> Now, let's head over to -- WAIT! Look over there. It's Dr. Kathy
> Flanders and Dr. Sharon Glynn talking in the hallway. I'm sure they
> won't mind if we ask them a few questions. Hello Doctors. I'm here
> with a few of my friends and we're trying to figure out what cancer
> really is. First off, where do you guys work?

**Flanders:** Well, my name is Kathy Flanders. I'm a staff scientist,
and I work in the Laboratory of Cancer Biology and Genetics at the NCI.

**Glynn:** Ok, My name is Sharon Glynn and I'm a cancer prevention
fellow at the NCI, and I specifically work in the breast and prostate
cancer group.

**Josh:** Nice answers, but now for the harder ones. What is cancer and
why does it make people so sick? Dr. Flanders, why don't you give it a
try?

**Flanders:** The basic problem is cells don't stop growing, but I think
in every tissue it is a little bit different. It's hard to say that this
one thing causes cancer and this is how we're going to fix it. It's
really, such a combination of lots of different little things that can
go wrong and it can be very tissue specific.

**Josh:** Dr. Glynn, do you have anything else to add?

**Glynn:** Cancer basically, in my own words, would be basically when
you get unregulated growth of a healthy part of the body, and so what
happens is that you have normal healthy cells, and then somehow, they
become what we call dis-regulated. They will grow uncontrollably; they
won't listen to the body's signals, because the body has a very tight
process that it keeps control of itself. So, generally when something
gets out of control, the body will actually signal to itself and tell it
to stop, and it will either stop the growth or will eliminate it
altogether. Somehow cancer cells, seem to kinda skip this process by.
Like depending on the cancer type, there are different kinds of pathways
it will follow, so like breast cancer, the primary tumor that develops
in the breast, that would not be what would kill the patient, rather
it's the actual spread when it spreads to other parts of the body. It
spreads to the lungs, and you know, you have to think about organs that
are vital for your survival, so you need your lungs for breathing, if it
spreads to the brain, obviously you need your brain. So depending on the
type of cancer.

**Josh:** Now, what are you currently working on in your labs?

**Glynn:** What I do is, we have cohorts; people who have volunteered
who are cancer patients who volunteered to enter into these studies, and
so they give us permission to take a sample of their tumor, and they
also answer questions about their family history, their lifestyle,
various different things like that. Then what I can do with that is I
can profile their tumors and I can try and see what takes one tumor,
take for example what makes one patient respond to chemotherapy and
other not. What makes one person survive and another person not survive?

**Josh:** And finally, what technology aids you in your research?

**Flanders:** I have an automated stainer that I can put 60 slides in,
program it, set it up, and it does the tedious work, and frees me to do
other things during the day. And then I have the fun part of going
though and looking at the tissues sections under the microscope and
trying to figure out what happened.

**Josh:** Amazing answers. We've learned a lot, but now we have to huff
it over to Building 10, the largest on campus, where we have a meeting
with Dr. Deborah Citrin, a radiation oncologist. Thanks Dr. Flanders and
Dr. Glynn.

*Drum Beats*

> So right now, we're in Building 10, but I have no idea where to go. It
> is pretty cool though that there are patient rooms in one hall and
> labs in the next. I guess they really mean it when they say bench to
> bedside. Let me ask the information desk over there for directions.
> Excuse me, can you point me in the direction of Dr. Citrin's office.

**Receptionist:** You make right at the end of this hall, then another
right, and then one more. Or you can just turn around, she's standing
right behind you.

**Josh:** Oh. Dr. Citrin thanks for meeting us. Dr. Citrin, what college
did you go to?

**Citrin:** I went to North Carolina State University in Raleigh, North
Carolina. Had a very wonderful time there; it's a great school.

**Josh:** What is the difference between a normal, healthy cell verses a
cancerous one?

**Citrin:** We don't completely understand all the differences but we
know that a lot of cancer cells tend to be more similar to very immature
cells in the body and what we describe that as is being less
differentiated. So very often they're more like cells that you would see
in an embryo or when an organ is just forming. Because of that they have
the ability to grow unchecked and can spiral out of control. They also
can go to other parts of your body and start doing the same sorts of
things in those areas.

**Josh:** Have you ever come across any major misconceptions about
cancer?

**Citrin:** One of the things that I hear a lot from patients is that
they are convinced as soon as they're diagnosed with cancer that they're
going to die. I think that that comes from the fact that a lot of
patients diagnosed 50 or 60 years ago didn't have a lot of treatment
options and the prognosis was much poorer for almost all patients who
had any sort of cancer. Today we have a lot more effective treatments
and several diseases we can look at more as chronic diseases instead of
cancer that is life threatening and terminal in a very short order.

**Josh:** You're a clinician right? What is a clinical trial and have
you ever worked on any before?

**Citrin:** So a clinical trial takes volunteers who know what the test
is about, or what the protocol will be testing, and those volunteers are
subjected to either a treatment or in some cases to a placebo and
they're followed for some period of time to see whether those treatments
or placebos have any effect on whatever disease is being treated. So, I
have a clinical trial where I'm treating patients who have metastatic
disease from a cancer, who have five or fewer sites of disease. Those
metastatic sites are treated with radiation, very high doses over a very
short period of time. The goal of this study is to see if we can treat
patients who have just a few sites of metastatic disease and result in
good control of those metastatic sites to where they will not grow and
cause discomfort. And, also, to see if those patients live longer than
patients with other sorts of metastatic diseases.

**Josh:** One final question, what do you see as some of the most
exciting frontiers and unanswered questions in cancer research?

**Citrin:** Most of us hope that we can one day take a piece of a tumor,
learn everything there is to know about it very quickly and then give
the patient the right drug based on that tumor's specific signature.
That same technology, those same drugs, those targeted agents, can be
very useful for the same purposes with radiation, to make the radiation
work better.

**Josh:** Thanks so much for speaking with us today Dr. Citrin, but now
we have to check out Dr. James Gulley. He's on the eleventh floor, so
let's take the elevator.

*Drum Beats*

> Hello Dr. Gulley. Thanks for showing interest in our quest. Let's
> start off with what got you into science and brought you to NIH?

**Gulley:** Well, I've always been interested in what makes things tick.
How things work, both in mechanical things, but as looking into the
human system, obviously a lot more complicated. And as I began
understanding or learning how things worked normally, it was fascinating
to me to see how cancer evolved and took this normal machinery and made
something bad out of it, and how you could turn that back into being
normal again.

**Josh:** Why'd you pick to come here?

**Gulley:** Yeah. NIH really is fascinating for several reasons. Number
one, you have a lot of resources. I don't just mean money, I mean
dedicated, intelligent people who really are interested in figuring out
what makes things work. They're here because they want to make a
difference, and they're not here just to make money. Otherwise, they
would probably be in different jobs.

**Josh:** Now, what is a cancerous cell?

**Gulley:** We have inbuilt into ourselves stop signals, so that when
you get to a certain size, you stop growing. Cancer cells, for one
reason or another do not have that checkpoint, so they start to grow,
and they continue to grow, they disregard all of the rules, and they
make a mess of themselves. Just like if we didn't obey the no
shoplifting, things would turn into mayhem pretty quickly, and that's
what's happening on a cellular level. Now obviously, to us as
individuals, cancer is a growth that you can feel, or see, either on the
skin or see in a CT scan of the body or with special x-rays.

**Josh:** What does cancer do to someone's body?

**Gulley:** Another good question. Various cancers do various things.
There are cancers like leukemias that are cancers of the blood cells
that go throughout the whole body and just kind of increase in number
and can make the blood really thick, and you can have strokes from that.
There are other cancers, what we call solid tumors, that grow large and
cause pain or pressure in a certain area or can go to vital organs and
cause damage to those, such as the lung, or the brain, or the kidneys,
or the liver, and cause those organs not to work very well.

**Josh:** You're a clinician just like Dr. Citrin. What are the
different stages of a clinical trial?

**Gulley:** Clinical trials basically are when you take a new drug or a
new combination of drugs and test them in humans. Usually, we refer to
clinical trials as either being phase one, phase two, or phase three.
There are others too, but let's just stick with those for now. Phase one
trials are the first time a drug has been tested in humans, or the first
time a combination has been tested in humans, or if that drug has been
tested before, but you are now trying it a different way or a different
method of giving it, either the route of administration, that would be
considered a phase one trial. The primary purpose of a phase one trial
is to see can you give this dose or the drug this way and not have too
many side effects from it. Then there's the phase two study. This is the
trial really designed to see if there is evidence that the drug is
working. So the first one is kind of can we give it safely in a small
group of patients? The second one is does it seem to work? And if it
seems to work, then we can go into the bigger trial, a phase three
trial, which is usually a comparative trial where you have the
experimental drug verses a control arm, which is usually a standard
treatment, and see which one is better.

**Josh:** And finally, do you have any advice for students considering a
career in science?

**Gulley:** My advice would be to study. Study hard. Learn as much as
you can about everything, not just about science, science is important.
That is the foundation for a career here, but for instance, English is
very important. You think, why English? Well, communication. If you can
communicate effectively in writing, you're gonna be a superstar in
science.

**Josh:** Dr. Gulley, thanks so much for taking your time to speak with
us. We're gonna take a quick break and recap all that we have just
learned. Thanks again Dr. Gulley.

*Drum Beats*

> I know we've learned a lot so far, so lets go over everything. From
> Dr. Flanders, we learned that cancer occurs when cells don't stop
> growing. Dr. Glynn mentioned that depending on the cancer and where it
> occurs, many different things can happen. Dr. Citrin pointed out that
> cancer cells resemble immature cells. And finally, Dr. Gulley defined
> the three phases of clinical trials and how at each phase, the number
> of participants increases. Now that we've summed those scientists up,
> lets meet a few more. Let's head back over to Building 10 and talk to
> Dr. Crystal Mackall, chief of the Pediatric Oncology Branch. Don't
> worry, this time I brought a map.

*Drum Beats*

> Hello Dr. Mackall, we were wondering if you wouldn't mind shedding
> some knowledge on pediatric oncology. First off, what are the
> different levels of doctors?

**Mackall:** A primary care doctor are those that are the front lines;
that most healthy people, if they need a doctor, they go to a primary
care doctor. It can be a pediatrician; for a young lady, it can be an
obstetric gynecologist for an annual exam; it can be an internist, if
you're perhaps an older person; it can be a family practitioner. They're
all on the front lines. If you then have a problem that requires more
specialized care, then you're referred to a specialist, and so that is a
secondary level. You usually think of a place like NIH as being more of
a tertiary, where you come for very, very specialized care.

**Josh:** In your perspective, what is cancer and how does the cancer
spread?

**Mackall:** Cancer is much more complex than that because it's your own
body that has turned and gone awry. And, it's not the kind of thing that
can happen very easily. Chances are that there are a lot of mistakes
that your body makes all the time as its cells are dividing and its
immune system develops, etc., but most mistakes don't matter. But, once
in a while -- and this is all a statistical probability -- a mistake
happens that gives one part of your body the wrong signal, and that
signal is one of inability to control its own growth. And yet, it still
retains the features of your own body and so your body mistakenly
doesn't recognize that it's a bad guy until it's too late. And it's hard
to find the Achilles' heel. We're always looking for the Achilles' heel;
that is, the weak spot that the cancer cell has that your normal cells
don't have. And it's never black and white; it's always a matter of
degree. It's very much like Darwin; if you've studied Darwin, this whole
notion of survival of the fittest; it actually pertains very well to
cancer. Because you end up with a cell that kind of becomes very selfish
and self-sustaining and starts to feed itself at the expense of others
and it becomes more fit that those around it and it outgrows and so you
end up with a tumor that is growing more quickly and is healthier than
the rest of the body. So, cancer is really just a genetic mistake, in my
mind, that results in an advantage to the cell that the rest of the body
can't stop.

**Josh:** You know so much Dr. Mackall. What college did you go to?

**Mackall:** I have a very unique pedigree for NIH. I like to use the
word pedigree. I went to the University of Akron, which is part of a
six-year medical program through the Northeastern Ohio University's
College of Medicine. So, my medical school was Northeastern Ohio
University's College of Medicine, the undergraduate portion was the
University of Akron, and I got my bachelor's and medical degree in six
years; went straight through summers and everything. So, it's an
interesting program; it's actually quite challenging. Its goal is to
create primary care doctors, so in some ways I'm a black sheep because
here I am in a tertiary care setting.

**Josh:** Can you offer any advice to us if we want to go into the field
of science?

**Mackall:** I think that everybody, regardless of whatever they want to
be when they grow up, should be offered and seek out opportunities to
explore science. Again, everybody's not going to be a scientist,
everybody's not going to be a physician, nor should they. But you know
what? Science is really the act of investigating our world and what's
more intriguing than understanding the world around us? Our bodies, our
environment; it's near and dear to all of us to learn more about our
world. And, so, really, science is really a matter of simply being
curious about the world around you, and I think regardless of whatever
you want to be when you grow up, there is some natural beauty that you
can appreciate if you spend the time to learn about the world around
you.

**Josh:** Dr. Mackall, thanks so much for talking with us. *Ring. Ring.*
Hey, I got a call coming in. Hello. Oh, hello Dr. Hunter. Yes, we are
trying to find the answer to what is cancer? You want to help us? Great!
We'll be right over. See ya. Ok guys. That was Dr. Kent Hunter, and he
said that he may be able to help us. Let's go. Thanks again Dr. Mackall.

> Boy was she nice. Let's hop on the bus to get to 37 'cause it's pretty
> hot out here.

*Drum Beats*

> Ok. We're here at Building 37. It's a lot smaller than Building 10 and
> I think Dr. Hunter's office is right down the hall. Here it is. Hello
> Dr. Hunter. Thanks so much for speaking with us. I won't waste your
> time; so let's get right into cancer. What college did you go to?

**Hunter:** I went to the Pennsylvania State University, Penn State. I
enjoyed it a lot. It was a lot of fun.

**Josh:** Ok. Now we'll get into cancer. Is cancer scary? Should we be
living in fear of cancer?

**Hunter:** Yes, cancer can be scary. Cancer is a scary thing. Anything
that is a life threatening disease is scary. Should we be terrified of
cancer? No, I don't think so. We should be careful, just like we are
with everything else. We should try to avoid situations that are
avoidable that cause cancer. One of the things that I think is important
is that people need to understand is that exposure to carcinogens is
really important. Smoking, for example, if we got people to stop smoking
that would solve a lot of the cancer, particularly lung cancer problems.

**Josh:** What are you currently working on in your lab?

**Hunter:** So what my laboratory works on is investigating how
inheritance affects whether or not the tumors will spread or not. In
breast cancer, which is the particular cancer that I work with, but also
with most other cancers, it's generally not the primary tumor that is
the cause of death. It is when the tumors spread to other parts of the
body. If the tumor stayed localized, in most cases we'd be able to solve
cancer by surgically resecting the tumor. But they spread, and we've
been trying to understand why it spreads and how it spreads, and what we
can do about it.

**Josh:** And finally, why should a high school student even consider a
career in cancer research?

**Hunter:** Well, it depends. For me it's very exciting. I get to sit
here everyday and peel apart the onion on how metastasis works. How many
layers there are; there's huge numbers of layers, but each day, I feel
that I am getting more information, I am helping to solve the puzzle,
and for me that is very satisfying. It also appeals to my altruistic
side, in which I am attempting and trying to contribute to human health
by developing more information and more knowledge about breast cancer
metastasis.

**Josh:** Dr. Hunter you have been amazing! I know that it's getting
late, but I've got one more scientist I went you to meet. Dr. Diane
Palmieri is only one flight down, so let's take the stairs

*Drum Beats*

> *Knock Knock.* Hello Dr. Palmieri. My name is Josh and these are my
> friends. Dr. Hunter said you could help us understand cancer. So, what
> got you into science and made you want to work for NIH?

**Palmieri:** Actually, I've wanted to be a scientist since I did my
first science project in the seventh grade, so I'm pretty much a science
geek. The first time I did a science project and I had to generate a
hypothesis, I did a whole genetic testing thing, where I tested members
of people's families and saw how inheritance patterns went on and I was
hooked from there on in and I wanted to be a scientist. And I wanted to
be a geneticist, cause I thought that was cool, cause that was the first
thing I learned about, DNA and all that. It wasn't I think until I was
probably applying to graduate school when I decided I wanted to do
cancer research.

**Josh:** So then what pulled you to NIH?

**Palmieri:** I wanted to get some experience after I finished graduate
school in the government and see what being a government scientist was
like, because as a graduate student you sort of understand what
academics would be like and a career of an academic scientist would be
like because they're the people that you work for and your mentors in
graduate school. And you kind of have a feel for industry in the fact
that you know how businesses are run, just from being part of the world.
The government seemed a little more nebulous as to how it all took place
because it wasn't an academic institution, so I wanted to come here
after graduate school to do my postdoctoral fellowship, just to see how
the NIH worked and how the government worked.

**Josh:** Before coming to NIH, what college did you go to?

**Palmieri:** I went to Rochester Institute of Technology in Rochester,
New York as an undergrad, and I went to the University of North Carolina
at Chapel Hill as a graduate student. Go Tarheels. Big Tarheel fan.

**Josh:** How does a cancerous cell arise?

**Palmieri:** Internal factors, I would say the biggest one as genetics.
Everyone will sort of tell you as a buzz phrase that cancer is a genetic
disease. Externally, there's obviously a lot of things that play into
cancer, and probably the biggest and most well known is cigarette
smoking and lung cancer.

**Josh:** Is there any way a person can truly prevent cancer?

**Palmieri:** I don't think you can prevent cancer. People can do things
in their lifestyle and in the course of their life to reduce their risk
of getting cancer, but I do not think it has ever been proven you can
actually prevent yourself from getting cancer.

**Josh:** What technology aids you in your research?

**Palmieri:** One thing we do is laser capture micro dissection. And
this is a laser that's hooked up to a microscope, so that you can put a
piece of tissue underneath a slide into the microscope, and you can use
the laser to actually capture or zap the specific cells in that tissue
that you want and remove them so you can just experiment on them. A lot
of times you get biopsy samples from patients and they might only have a
few tumor cells in them and they might have a lot of normal tissue
because a biopsy punches just a couple of millimeters of a needle that
they stick into someone's tumor. You could grind the whole biopsy sample
up and do experiments on it, but then you're mostly experimenting on
normal tissue. And so, by using the laser capture micro dissection
machine, you can actually pick the specific tumor cells out and avoid
the normal tissue, so you can concentrate on the normal tumor cells.

**Josh:** Thanks so much Dr. Palmieri! I think it's time for another
recap on the last three scientists.

*Drum Beats*

> From Dr. Mackall, we heard about the different levels of doctors.
> Primary care doctors are those who we see to get our annual check-ups
> and tertiary doctors, like Dr. Mackall, are those we see if we need
> extra special attention. Dr. Hunter says that cancer is scary and we
> should be aware of it, but not let it ruin our lives. And finally, Dr.
> Palmieri talked about a laser dissection microscope that cuts out
> specific cells. How cool!

*Drum Beats*

> And that pretty much wraps it up. We have been to eight scientists,
> including the director of the National Cancer Institute, and learned
> so much about cancer. I would like to thank Dr. Niederhuber, Dr.
> Flanders, Dr. Glynn, Dr. Citrin, Dr. Gulley, Dr. Mackall, Dr. Hunter,
> Dr. Palmieri, Dr. Bennett and all those at the National Cancer
> Institute. For those of you who would like to learn more about these
> scientists or just more about cancer, then log on to
> www.ccrr.cancer.gov. *Music Playing* From the NIH campus in Bethesda,
> Maryland, this is Josh Oppenheimer saying, get out there and spread
> your newfound knowledge. See ya!

Created By: Josh Oppenheimer July 2008