February 11, 2025 • 30 mins
On this episode, we will hear from medical oncologist, Dr. Dawn Lemmane about her pioneering work in applying mathematical principles to cancer treatment. In doing so, Dr. Lemmane and her team are leading the way in understanding how to personalize cancer treatment to maximize tolerance and curative benefits.
Five To Thrive Live is broadcast live Tuesdays at 7PM ET and Music on W4CS Radio – The Cancer Support Network (www.w4cy.com) part of Talk 4 Radio (www.talk4radio.com) on the Talk 4 Media Network (www.talk4media.com).
Five To Thrive Live Podcast is also available on Talk 4 Media (www.talk4media.com), Talk 4 Podcasting (www.talk4podcasting.com), iHeartRadio, Amazon Music, Pandora, Spotify, Audible, and over 100 other podcast outlets.
Five To Thrive Live is broadcast live Tuesdays at 7PM ET and Music on W4CS Radio – The Cancer Support Network (www.w4cy.com) part of Talk 4 Radio (www.talk4radio.com) on the Talk 4 Media Network (www.talk4media.com).
Five To Thrive Live Podcast is also available on Talk 4 Media (www.talk4media.com), Talk 4 Podcasting (www.talk4podcasting.com), iHeartRadio, Amazon Music, Pandora, Spotify, Audible, and over 100 other podcast outlets.
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Episode Transcript
Available transcripts are automatically generated. Complete accuracy is not guaranteed.
Speaker 1 (00:00):
Any health related information on the following show provides general
information only. Content presented on any show by any host
or guest should not be substituted for a doctor's advice.
Always consult your physician before beginning any new diet, exercise,
or treatment program.
Speaker 2 (00:40):
Welcome to five to Thrive Live, a podcast about thriving
for those who have been affected by cancer and chronic disease.
I'm doctor Lisa Schuler and I co host with my
good friend Carolyn Gazella. You can find all of our
past show podcasts on every major podcast outlet and the
schedule on ithriveplan dot com. I will be talking with
(01:01):
doctor don Lemon about the amazing intersection of mathematics, nature
and treating cancer. She's going to take us into this.
Doctor Don Leman is a Stanford trained board surfied oncologist
specializing in complex oncology. She focuses on patients with advanced
treatment resistant cancers, integrating conventional treatments with evidence based strategies
(01:25):
like diet, exercise, sleep optimization, botanicals, and mathematically informed drug
scheduling to improve outcomes and reduce toxicity. In fact, she
and her team recently won first prize in funding in
an international mathematical oncology competition for their work in the
intersection of the microbiome and cancer treatment efficacy. Doctor Lemann
(01:49):
practices at Oregon Integrative Oncology and Ashland, Oregon, and is
clinical assistant professor at the University of Arizona's Andrew Wild
Center for Integrative Medicine. Where we start a conversation with
doctor Leman, I want to talk. I want to thank
our sponsors. First, we have Amuse, a unique patented post
biotic that gives your immune system a key advantage. Amuse
(02:11):
is an ingredient in many immune supporting dietary supplements, so
look for Amuse on the label or go to immusehealth
dot com. Also cognizance aticoline, which is nature's way of
keeping the brain's energy producing centers firing in all cylinders.
So if you want to enhance your brain function, memory, focus,
and attention, look for Cognizant on the label or go
to cognizant dot com for more information. And in fact,
(02:35):
Prothriver's Brain is a product that contains Cognizant as well
as other brain supporting nutrients and herbs, and you can
find pro Thriver's Brain online at pure Formulas dot com.
Finally a doctor or Heroes Probiotics, a best selling probiotic
for over thirty years, which contains twelve probiotic strains that
are shelf stable without refrigeration due to their unique three
(02:58):
year fermentation system. You can learn more at doctor Ohira
Probiotics dot com. Doctor Leman, welcome to five to Thive Life.
Do you say Leman or Laman?
Speaker 3 (03:08):
I say either one. I think more people say Leman,
So take your pick and I will answer.
Speaker 2 (03:14):
Okay, well I did both, So welcome to the show.
Speaker 3 (03:17):
Thank you, Lisa's doctor Alschuelder. Shall I call you that?
It's I'm so used to calling you Lese because we
work together at the Wild Center.
Speaker 2 (03:26):
Yeah, we can go buy our first name. So I
just like to introduce you right up front as the
doctor is that you've you know, worked so hard to
earn and be well, you know. In fact, on that note,
maybe you can start by introducing yourself a bit more
to our listeners and just tell us a little bit
about how you became interested in medical oncology and then
integrated oncology.
Speaker 3 (03:48):
Yeah, so I've always been interested in how diet and
exercise and sleep and other health habits intersect with cancer,
and when I was a kid, cancer touched my life.
Not directly. It wasn't in my family, but I had
(04:08):
several playmates who actually succumbed to childhood cancer, and I
wondered what this disease was, why it was so untreatable.
In those days, it was very difficult to find a
cure for cancer for anyone, and I took that with
(04:29):
me into my college and adult years. I wanted to
be a doctor. From I don't know the age of
seven or so, I knew that was what I was
going to do. And I'm a little bit older than you,
lease and had I been younger, maybe your age, I
think I might have become a nature path. But I
went into college and then to conventional medical school, taking
(04:54):
this particular interest with me very strongly. So I consider
that I've always been in a greater oncologists although I've
gone through and gotten all of the credentials for regular
standard medical oncology, and I do practice medical oncology in
the sense that I do prescribe chemotherapy and hormonal therapy
(05:15):
and all of the things, and I work with radiation
oncologists and surgical oncologists with my cancer patients. But I
also incorporate all of the lifestyle and personal things that
people can do in the treatment plan and make sure
that we take advantage of everything that we possibly can
(05:36):
to get people.
Speaker 2 (05:37):
Well. Yeah, absolutely, Well, we're glad you do what you do,
and you're really a pioneer in many ways. In one
of the areas that you're pioneering is this idea of
adaptive cancer therapy. So let's maybe start by describing what
adaptive cancer therapy is and particularly how that's different than
(05:57):
the typical conventional cancer therapy that most people are receiving.
Speaker 3 (06:02):
You know, adaptive means you change depending on the circumstances,
and adaptive cancer therapy changes depending on the progress or
lack thereof in the treatment of the patient. So specifically,
I'm going to take a step back and describe why
we would want to even think about something like this.
(06:24):
And if your listeners, your listeners will will know everyone
knows and has been close to someone who's gotten a
diagnosis of cancer, and the oncologists may say something like, well,
you know, it's not curable, but it's treatable, and so
(06:45):
treatment commences and lo and behold, the scans do improve,
the tumor markers improve, everything looks better, and for a
few months, wow things, you know, things, things are looking
like we're making some progress. But then the progress slows
(07:06):
and then stops. The scans start reversing, and the tumor
markers go up again, and pretty soon you're back to
where you started, and the doctors will say, well, the
treatment has stopped working, so we're going to go on
to another treatment. And the second treatment is applied, and
the same thing happens, typically with a faster course. So
(07:26):
if it took you know, twelve months to get to
that point with the first round of treatment, typically the
second round is three to six months, and the third
round maybe one point five to three months something like that.
We usually we often go down by half and pretty
soon no treatment works and the patient ends up going
in hospice and the end comes. So that is the
(07:49):
standard path for patients with many, many advanced cancers in
this country. The types of cancers that aren't curable with
standard therapy is now there are cancers that are curable
with standard therapy, and if that's the case, this discussion
is not applicable to that. So I want your listeners
(08:10):
to understand that if your doctor says, you know, we
can cure you with standard therapy, that's you know, that's
what you should do. But if the doctor says, well,
we can't cure you with standard therapy, those are often
the patients that will come to me and say, you know,
can we try this adaptive approach? And what an adaptive
approach does is it tries to circumvent this particular scenario.
(08:35):
So what happens in this scenario when you treat a
cancer patient with a large high dose of medication right
up front, all of the cancer cells that are sensitive
to that medication die off. That makes sense, right. The
ones that are left, however, and there are always some
left are just by definition resistant to that treatment. That
treatment didn't affect them. They're still there and they're not
(08:58):
just biding their time and waiting. They're actively continuing to grow.
So while the overall tumor situation is shrinking, that particular
small population of cells is continuing to grow and eventually
it repopulates the entire tumor and the scenario that we
just discussed plays out, so can that process. That process
(09:20):
is called the development of treatment resistance, And what's developing
treatment resistance is not the patient. It's not the patient
that's becoming resistant to the treatment, it's the cancer cells
that that patient is harboring. So is there anything that
we can do to prevent the cancer cells from developing
treatment resistance? An answer actually comes from ecology, from environmental science.
(09:45):
So in the fifties, there was a call it a
drug how my mind works, but it was a pesticide
called DDT was developed around nineteen fifty. It started to
be applied to the cotton crop in the South. Cotton
in the south of the United States is a major
economic force, and when a pest called the cotton bowl
(10:07):
weavil started destroying the crop, it was a big problem.
And so in the early nineteen fifties, DDT was developed
and applied every year for three, four or five years
to the cotton crops in the southern United States, and
lo and behold, the bowl weavils just went away. Well,
after about four or five years, there started to be
(10:28):
some bowl weavils coming back, and I think, I hope
this story sounds familiar. And after six or seven years,
the bowl weevils were back in force, and maybe even
a little worse, and all the DDT in the world
being applied, and there was a lot being applied didn't
affect them. They were not sensitive to this. So wele
(10:51):
oncologists finally started to learn from that particular field, and
a lot of environmentalists were recruited about many years ago
into the cancer research effort, and environmentalists and also physicists
were recruited by the National Cancer Institute to try to
make some headway in cancer and one of the major
(11:13):
centers of that was just up the road in Phoenix
at Arizona State University. One of the leaders of that
was a physicist named Paul Davies, and he and other
workers put the mathematics of physics and environmental mathematical mathematical
(11:38):
techniques to work in the field of oncology and figured
out that evolution Darwinian processes are driving the development of
treatment resistance. And the way that agriculturists got around that
was to diversify the ways that they dealt with pests,
(11:58):
so not only just applying a pesticide, but also rotating crops,
planting crops that had a symbiotic effect with each other
and would help control the pests. Those kinds of things.
Those kinds of things were then applied in the laboratory,
of course to cancer models and were found to be useful.
(12:19):
And the backbone of this research was actually mathematics, so
that's where this whole idea came from. What it looks
like in the clinic is if we have a patient
who has a tumor that is sensitive to a particular drug,
we apply that drug just enough to take away the
(12:43):
patient's symptoms, not enough to push the tumor markers down
to zero. We try to avoid that, and not enough
to make the cancer go away as best we can
tell on our scans, and in fact, we try to
keep a lot of the cancer cells around, and we
try to keep the cancer cells around specifically that are
(13:04):
sensitive to our treatment. And the way that we do
that is we measure if the patient has a tumor
marker a blood marker for instance, like prostate cancer is
a great example because a lot of prostate cancer patients
have a blood marker called the PSA prostate specific antigen.
So we can watch that antigen and if we are
(13:26):
able to see how fast the PSA drops with our
treatment that the tumor is sensitive to, and then we
remove the treatment and let the cancer grow back somewhat
and see how fast it grows back. We can determine
an ideal dosing pulse length that maintains some cells in
(13:53):
the treatment sensitive compartment we call it of the cancer,
and those cells, interestingly enough, actually suppress the treatment resistant
cells in that cancer. And the way they do that
is they outcompete them for nutrients, waste removal, oxygen, those
kinds of things. So I hope that at least as
(14:16):
a start explaining what adaptive therapy is, it's pulse to
treatment based on specific timing of tumor growth and regression
in the presence and absence of a drug that the
tumor is sensitive to.
Speaker 2 (14:34):
So in that description you mentioned that at least initially,
you only want enough of the tumor destroyed to help
you model it, to help you understand how fast, how
sensitive the tumor is to this particular chemotherapeutic and how
fast the tumor responds. Eventually, with that information, do you
(14:57):
continue to apply sort of maybe so total lethal doses
or and are you just managing the cancers of chronic
disease or are you seeking to eventually eradicate the tumor?
Speaker 3 (15:10):
Holy so that's a great question. So we do measure
the tumor dynamics off and on treatment at the beginning
of the adaptive treatment protocol, but we're also not just
looking to measure the tumor dynamics. We're also trying to
get the patient to an asymptomatic state. So we want
the patient to feel better throughout this process and to
(15:31):
feel well. And the idea is to yes to have
the tumor become a chronic disease that waxes and wanes
but remains below a symptom threshold. And the other idea
is to make sure that we don't decrease the tumor
(15:52):
as much as we can. So the last thing you
want to do in an adaptive protocol is try to
suppress the tumor as much as possible, make the scans perfect,
make the tumor markers go down to zero or close
to zero. Those actually speed the development of resistance, so
we don't try to do that. What will typically do
(16:13):
a common number that we will aim for, and this
is not in everybody because again this is very personalized,
but we'll aim to take the tumor marker down no
more than fifty percent maybe twenty five percent from where
we started. So let's say to make these round numbers,
(16:33):
we might have a PSA starting at one hundred. We
might treat to a PSA of fifty or twenty five
something like that. We certainly don't try to go down
to five or three or points something never. And again,
the reason for that is that the more vigorously you
treat these tumors and the farther you push them down,
(16:53):
the more rapidly you produce a treatment resistant tumor situation. Now,
having said that, you know, can we ever get to
a cure with this? And by cure I'm going to
define that as the disease goes away and never comes back.
There are some interesting findings from pilot studies at Moffitt
(17:16):
Cancer Center in Florida with prostate cancer patients. After five
to eight years, some of the patients started on an
adaptive protocol seemed to when they've been taken off there,
when they've been given a treatment holiday in the adaptive protocol,
sometimes the PSA has not risen again, it has stayed low,
(17:39):
and those patients may be cured. We don't know yet.
We have to you know, the data aren't mature. We
have to see what happens to those patients over many years.
But that was very encouraging and a surprise actually to
see that. Yes, perhaps in some cases this process led
to an even better outcome than we we thought it might.
Speaker 2 (18:04):
Yeah, it's just very interesting. It's so different than everything
else about oncology, which is, you know, of course, to
eradicate the tumor as quickly and as completely as possible.
Speaker 3 (18:16):
So how do you Well, I do want to say
that in a curative situation, that is exactly what you
want to do. So if the doctor, the oncologists again says,
you know, we can eradicate this tumor, then you do
want to hit it hard and fast and as you know,
as quickly and as thoroughly as possible. That's a different scenario.
So again, the adaptive approach would not be appropriate in
(18:38):
that kind of situation. MH.
Speaker 2 (18:41):
So, I think you've kind of touched on this, maybe
without using the terminology, but you talk about cellular senescence
and that being a predictor of treatment toxicity. So can
you talk a little bit about what that is and
how you use that to improve your outcomes and treatment tolerance.
Speaker 3 (18:58):
Sure, we don't know yet, So the research award that
my team was granted last month actually is going to
look into that. So we believe from animal studies that
cellular senescence can predict treatment toxicity. And what cellular senessence
(19:20):
is is the normal aging of cells. Happens with years.
It can also happen with exposure to toxins, radiation, things
like that. Anything that damages cellular DNA can lead to
what's called cellular sedesence, which is the arrest of the
growth cycle. So if a cell it has been damaged
(19:41):
beyond repair, it will never divide again. The division machinery
is blocked and turned off, and that cell may stay alive,
but it just sits there and doesn't reproduce. That may
be a good thing, we think in many cases. We
think that these are cells that might otherwise become cancers
because of the damage that they've entertained. But the problem
(20:06):
with SINESM cells is that they will also elaborate some
something called the sinesence associated They will put out cytokines
and inflammatory molecules that can affect surrounding tissues and maybe
even the whole body. So they're not a great It's
not a great thing to have a lot of sinessem
(20:28):
cells around if you kill off sinesm cells, and there
are medications and you know, certainly natural substances like physetin
and quersotin and some drugs that can kill off sinesm cells,
but if you do too much of that, you kind
of deplete your stem cell pool and so you may
have some frailty issues with that. So it's kind of
(20:50):
a dilemma. One of the things that we've found is
that sinessence, especially in blood cells, may predict an inability
to tolerate right high dose chemotherapy and other types of
therapy cancer therapy as well. So we're one of the
things that we're going to look at is is that true,
(21:10):
and how does that work? And can we predict based
on certain patterns of sin essence in cells whether we
might need to back off on, you know, certain types
of treatment in certain patients. It's hard to tell which
patients are going to you know, a lot of patients
do very very well with their very strong cancer UH medications.
(21:34):
Some patients, however, have really horrible problems side effects. If
we could predict ahead of time who those patients might be,
we can of course, modify their their treatment and also
be ready with treatments for the side effects a little
sooner than we might be otherwise.
Speaker 2 (21:55):
And your present is also about the role of the
gut microbiome, so this is a whole new l to
this and how does how do you incorporate the gut
microbiome into this modeling that you're using.
Speaker 3 (22:08):
Sure, so one of the things that we've gotten a
grant to study is how the gut microbiome changes with
chemotherapy in a very organized way, and that's not been done.
That kind of research hasn't been hasn't been done very much,
so we're really proud of that. It's it's a new
way to look at cancer and treatment toxicity. So we
(22:28):
do know that that cancer treatments affect the microbiome. We
are going to make an organized inquiry into how the
gut microbiome is damaged throughout the course of chemotherapy in
ovarian cancer specifically, and we hope that that information eventually
(22:51):
can be used to both predict and moderate chemotherapy toxicity
in those patients. And so we suspect we don't know
we're going to look into this. We suspect that if
we can keep the microbiome in good shape, and if
we figure out how to do that, we will be
able to make the cancer treatment work better. Otherwise, we
(23:13):
think patients will have a better chance of getting well
if we can keep their gut in good shape.
Speaker 2 (23:21):
Yes, indeed. Well, I'm wondering what you think is this
revolutionary stuff? I mean, is this going to completely change
the way that cancer care is delivered or is this
sort of something that you see is going to play
a role but maybe not really make it into the
big time.
Speaker 3 (23:42):
I think it's already in the big time, and I
think it will be very revolutionary. I think the idea
that we can improve the way we actually administer drugs
by changing the schedule is really is revolutionary. So there
are a lot of rhythms in nature, and so far
we've as a as a group I'm talking about doctors, uh,
(24:05):
medical oncologists, we've ignored those rhythms quite a bit. So
there are rhythms to the best times to give treatments,
there are rhythms to the best time to test and
inter act with the microbiome, those kinds of things, and
that's one of the things that we haven't been able
to look at until now when we have new ways
(24:28):
of looking at the gut metabolomics, proteomics, those things can
be checked frequently, and we are doing that now, and
we see these huge fluxes in the gut microbiome over
the course of you know, minutes and you know, certainly
(24:49):
hours and days. And we've looked at you know, microbiome
snapshots you know, maybe once or twice a year, and
we may sure not that we have to look several
times a day or something like that to really be
able to manipulate and take advantage of the rhythms there
for patient well being and healing.
Speaker 2 (25:11):
Mm So do you think adaptive therapy what will it
take to bring this adaptive therapy type of treatment to
patient care in most patient care centers, Because I mean,
I think it's it's available, but it's not easy to find.
Speaker 3 (25:29):
You know. I don't know of any place outside of
academia accept my practice that is actually actively doing this.
There may be other on coologists who are doing this privately,
but certainly larger academic centers are now taking a look
at it. I think Moffatt was one of the first
Arizona State University up the street is also one of
(25:53):
the leaders in evolutionary oncology. I'm a member of the
Americans as you for Cancer Research Working Group on Cancer Evolution,
and there are leaders from many wonderful institutions there who
are starting to take notice of this and working to
(26:17):
study it and to apply it to patient care. So
I do think, you know, in ten years, it will
be standard to use adaptive protocols in many of these cancers, okay,
And I think it will be standard to at least
look at the microbiome and attempt to intervene, you know,
(26:40):
when when it's damaged by treatment or just from life
or by the cancer itself.
Speaker 2 (26:45):
Right, Yeah, Okay, Well I'm gonna hold you to that.
So any last minute final thoughts you'd like to leave
with our listeners.
Speaker 3 (26:54):
Yeah. So, so, you know, there are some you know,
more it's not better in terms of advanced cancer treatment
and always, and I think that's something that needs to
be kind of shouted from the mountaintops that you know,
but just giving low dose there used to be something
(27:17):
called metronomic chemotherapy, which was basically giving a low dose
of chemotherapy and maybe giving it based on you know,
a calendar type of schedule like once a week or
you know, something like that. That doesn't work very well.
Either it worked every it worked occasionally, and that's why
it kept caught on. Every now and then a patient
would get better. And what the reason is is we've
(27:38):
found is that that's those are the patients whose tumors
accidentally matched the calendar. Most patients don't. Everybody's tumor has
a different growth rate. Tumor growth rates can change from
different seasons. They change across the course of the day.
For instance, tumors tend to grow faster at night. So
so all these things I think, uh, you know, I
(28:00):
want people to to to open their minds and understand that,
you know, the mathematics and cycles of nature play a
big role in all of nature, including cancer growth. And
as we unlock these, uh, the ways that these things work,
we can treat patients with a lot more skill.
Speaker 2 (28:22):
Amazing, Well, continue your good work, and how do our
listeners find you? Can you give us a website?
Speaker 3 (28:28):
So I have a website. It's called Oregon Integrative Oncology
and the u r L is based on that name,
and the u r L is Oregon like the state
O R E G O n IO dot com and
I also have a podcast called Docs Talk Shop and
(28:49):
you can listen to to that on any of the
major podcasts outlet and I do have some some episode
that go into detail on adaptive therapy.
Speaker 2 (29:03):
Great well, thank you so much, Don, It's really been
a pleasure talking with you. And keep up your good work.
I'll keep an eye on it for sure. And that
wraps up this episode of five to Thrive Live. We
thank our sponsors Cognizance of Cooline for memory, focus and attention,
Immuse post Biotic for immune support, Doctor Hires Probiotics award
(29:24):
winning pre and probiotic formulas and pro Thrivers wellness supplements
designed specifically for thrivers. May you experience joy, laughter and love.
It's time to thrive everyone, have a great night.
Any health related information on the following show provides general
information only. Content presented on any show by any host
or guest should not be substituted for a doctor's advice.
Always consult your physician before beginning any new diet, exercise,
or treatment program.
Speaker 2 (00:40):
Welcome to five to Thrive Live, a podcast about thriving
for those who have been affected by cancer and chronic disease.
I'm doctor Lisa Schuler and I co host with my
good friend Carolyn Gazella. You can find all of our
past show podcasts on every major podcast outlet and the
schedule on ithriveplan dot com. I will be talking with
(01:01):
doctor don Lemon about the amazing intersection of mathematics, nature
and treating cancer. She's going to take us into this.
Doctor Don Leman is a Stanford trained board surfied oncologist
specializing in complex oncology. She focuses on patients with advanced
treatment resistant cancers, integrating conventional treatments with evidence based strategies
(01:25):
like diet, exercise, sleep optimization, botanicals, and mathematically informed drug
scheduling to improve outcomes and reduce toxicity. In fact, she
and her team recently won first prize in funding in
an international mathematical oncology competition for their work in the
intersection of the microbiome and cancer treatment efficacy. Doctor Lemann
(01:49):
practices at Oregon Integrative Oncology and Ashland, Oregon, and is
clinical assistant professor at the University of Arizona's Andrew Wild
Center for Integrative Medicine. Where we start a conversation with
doctor Leman, I want to talk. I want to thank
our sponsors. First, we have Amuse, a unique patented post
biotic that gives your immune system a key advantage. Amuse
(02:11):
is an ingredient in many immune supporting dietary supplements, so
look for Amuse on the label or go to immusehealth
dot com. Also cognizance aticoline, which is nature's way of
keeping the brain's energy producing centers firing in all cylinders.
So if you want to enhance your brain function, memory, focus,
and attention, look for Cognizant on the label or go
to cognizant dot com for more information. And in fact,
(02:35):
Prothriver's Brain is a product that contains Cognizant as well
as other brain supporting nutrients and herbs, and you can
find pro Thriver's Brain online at pure Formulas dot com.
Finally a doctor or Heroes Probiotics, a best selling probiotic
for over thirty years, which contains twelve probiotic strains that
are shelf stable without refrigeration due to their unique three
(02:58):
year fermentation system. You can learn more at doctor Ohira
Probiotics dot com. Doctor Leman, welcome to five to Thive Life.
Do you say Leman or Laman?
Speaker 3 (03:08):
I say either one. I think more people say Leman,
So take your pick and I will answer.
Speaker 2 (03:14):
Okay, well I did both, So welcome to the show.
Speaker 3 (03:17):
Thank you, Lisa's doctor Alschuelder. Shall I call you that?
It's I'm so used to calling you Lese because we
work together at the Wild Center.
Speaker 2 (03:26):
Yeah, we can go buy our first name. So I
just like to introduce you right up front as the
doctor is that you've you know, worked so hard to
earn and be well, you know. In fact, on that note,
maybe you can start by introducing yourself a bit more
to our listeners and just tell us a little bit
about how you became interested in medical oncology and then
integrated oncology.
Speaker 3 (03:48):
Yeah, so I've always been interested in how diet and
exercise and sleep and other health habits intersect with cancer,
and when I was a kid, cancer touched my life.
Not directly. It wasn't in my family, but I had
(04:08):
several playmates who actually succumbed to childhood cancer, and I
wondered what this disease was, why it was so untreatable.
In those days, it was very difficult to find a
cure for cancer for anyone, and I took that with
(04:29):
me into my college and adult years. I wanted to
be a doctor. From I don't know the age of
seven or so, I knew that was what I was
going to do. And I'm a little bit older than you,
lease and had I been younger, maybe your age, I
think I might have become a nature path. But I
went into college and then to conventional medical school, taking
(04:54):
this particular interest with me very strongly. So I consider
that I've always been in a greater oncologists although I've
gone through and gotten all of the credentials for regular
standard medical oncology, and I do practice medical oncology in
the sense that I do prescribe chemotherapy and hormonal therapy
(05:15):
and all of the things, and I work with radiation
oncologists and surgical oncologists with my cancer patients. But I
also incorporate all of the lifestyle and personal things that
people can do in the treatment plan and make sure
that we take advantage of everything that we possibly can
(05:36):
to get people.
Speaker 2 (05:37):
Well. Yeah, absolutely, Well, we're glad you do what you do,
and you're really a pioneer in many ways. In one
of the areas that you're pioneering is this idea of
adaptive cancer therapy. So let's maybe start by describing what
adaptive cancer therapy is and particularly how that's different than
(05:57):
the typical conventional cancer therapy that most people are receiving.
Speaker 3 (06:02):
You know, adaptive means you change depending on the circumstances,
and adaptive cancer therapy changes depending on the progress or
lack thereof in the treatment of the patient. So specifically,
I'm going to take a step back and describe why
we would want to even think about something like this.
(06:24):
And if your listeners, your listeners will will know everyone
knows and has been close to someone who's gotten a
diagnosis of cancer, and the oncologists may say something like, well,
you know, it's not curable, but it's treatable, and so
(06:45):
treatment commences and lo and behold, the scans do improve,
the tumor markers improve, everything looks better, and for a
few months, wow things, you know, things, things are looking
like we're making some progress. But then the progress slows
(07:06):
and then stops. The scans start reversing, and the tumor
markers go up again, and pretty soon you're back to
where you started, and the doctors will say, well, the
treatment has stopped working, so we're going to go on
to another treatment. And the second treatment is applied, and
the same thing happens, typically with a faster course. So
(07:26):
if it took you know, twelve months to get to
that point with the first round of treatment, typically the
second round is three to six months, and the third
round maybe one point five to three months something like that.
We usually we often go down by half and pretty
soon no treatment works and the patient ends up going
in hospice and the end comes. So that is the
(07:49):
standard path for patients with many, many advanced cancers in
this country. The types of cancers that aren't curable with
standard therapy is now there are cancers that are curable
with standard therapy, and if that's the case, this discussion
is not applicable to that. So I want your listeners
(08:10):
to understand that if your doctor says, you know, we
can cure you with standard therapy, that's you know, that's
what you should do. But if the doctor says, well,
we can't cure you with standard therapy, those are often
the patients that will come to me and say, you know,
can we try this adaptive approach? And what an adaptive
approach does is it tries to circumvent this particular scenario.
(08:35):
So what happens in this scenario when you treat a
cancer patient with a large high dose of medication right
up front, all of the cancer cells that are sensitive
to that medication die off. That makes sense, right. The
ones that are left, however, and there are always some
left are just by definition resistant to that treatment. That
treatment didn't affect them. They're still there and they're not
(08:58):
just biding their time and waiting. They're actively continuing to grow.
So while the overall tumor situation is shrinking, that particular
small population of cells is continuing to grow and eventually
it repopulates the entire tumor and the scenario that we
just discussed plays out, so can that process. That process
(09:20):
is called the development of treatment resistance, And what's developing
treatment resistance is not the patient. It's not the patient
that's becoming resistant to the treatment, it's the cancer cells
that that patient is harboring. So is there anything that
we can do to prevent the cancer cells from developing
treatment resistance? An answer actually comes from ecology, from environmental science.
(09:45):
So in the fifties, there was a call it a
drug how my mind works, but it was a pesticide
called DDT was developed around nineteen fifty. It started to
be applied to the cotton crop in the South. Cotton
in the south of the United States is a major
economic force, and when a pest called the cotton bowl
(10:07):
weavil started destroying the crop, it was a big problem.
And so in the early nineteen fifties, DDT was developed
and applied every year for three, four or five years
to the cotton crops in the southern United States, and
lo and behold, the bowl weavils just went away. Well,
after about four or five years, there started to be
(10:28):
some bowl weavils coming back, and I think, I hope
this story sounds familiar. And after six or seven years,
the bowl weevils were back in force, and maybe even
a little worse, and all the DDT in the world
being applied, and there was a lot being applied didn't
affect them. They were not sensitive to this. So wele
(10:51):
oncologists finally started to learn from that particular field, and
a lot of environmentalists were recruited about many years ago
into the cancer research effort, and environmentalists and also physicists
were recruited by the National Cancer Institute to try to
make some headway in cancer and one of the major
(11:13):
centers of that was just up the road in Phoenix
at Arizona State University. One of the leaders of that
was a physicist named Paul Davies, and he and other
workers put the mathematics of physics and environmental mathematical mathematical
(11:38):
techniques to work in the field of oncology and figured
out that evolution Darwinian processes are driving the development of
treatment resistance. And the way that agriculturists got around that
was to diversify the ways that they dealt with pests,
(11:58):
so not only just applying a pesticide, but also rotating crops,
planting crops that had a symbiotic effect with each other
and would help control the pests. Those kinds of things.
Those kinds of things were then applied in the laboratory,
of course to cancer models and were found to be useful.
(12:19):
And the backbone of this research was actually mathematics, so
that's where this whole idea came from. What it looks
like in the clinic is if we have a patient
who has a tumor that is sensitive to a particular drug,
we apply that drug just enough to take away the
(12:43):
patient's symptoms, not enough to push the tumor markers down
to zero. We try to avoid that, and not enough
to make the cancer go away as best we can
tell on our scans, and in fact, we try to
keep a lot of the cancer cells around, and we
try to keep the cancer cells around specifically that are
(13:04):
sensitive to our treatment. And the way that we do
that is we measure if the patient has a tumor
marker a blood marker for instance, like prostate cancer is
a great example because a lot of prostate cancer patients
have a blood marker called the PSA prostate specific antigen.
So we can watch that antigen and if we are
(13:26):
able to see how fast the PSA drops with our
treatment that the tumor is sensitive to, and then we
remove the treatment and let the cancer grow back somewhat
and see how fast it grows back. We can determine
an ideal dosing pulse length that maintains some cells in
(13:53):
the treatment sensitive compartment we call it of the cancer,
and those cells, interestingly enough, actually suppress the treatment resistant
cells in that cancer. And the way they do that
is they outcompete them for nutrients, waste removal, oxygen, those
kinds of things. So I hope that at least as
(14:16):
a start explaining what adaptive therapy is, it's pulse to
treatment based on specific timing of tumor growth and regression
in the presence and absence of a drug that the
tumor is sensitive to.
Speaker 2 (14:34):
So in that description you mentioned that at least initially,
you only want enough of the tumor destroyed to help
you model it, to help you understand how fast, how
sensitive the tumor is to this particular chemotherapeutic and how
fast the tumor responds. Eventually, with that information, do you
(14:57):
continue to apply sort of maybe so total lethal doses
or and are you just managing the cancers of chronic
disease or are you seeking to eventually eradicate the tumor?
Speaker 3 (15:10):
Holy so that's a great question. So we do measure
the tumor dynamics off and on treatment at the beginning
of the adaptive treatment protocol, but we're also not just
looking to measure the tumor dynamics. We're also trying to
get the patient to an asymptomatic state. So we want
the patient to feel better throughout this process and to
(15:31):
feel well. And the idea is to yes to have
the tumor become a chronic disease that waxes and wanes
but remains below a symptom threshold. And the other idea
is to make sure that we don't decrease the tumor
(15:52):
as much as we can. So the last thing you
want to do in an adaptive protocol is try to
suppress the tumor as much as possible, make the scans perfect,
make the tumor markers go down to zero or close
to zero. Those actually speed the development of resistance, so
we don't try to do that. What will typically do
(16:13):
a common number that we will aim for, and this
is not in everybody because again this is very personalized,
but we'll aim to take the tumor marker down no
more than fifty percent maybe twenty five percent from where
we started. So let's say to make these round numbers,
(16:33):
we might have a PSA starting at one hundred. We
might treat to a PSA of fifty or twenty five
something like that. We certainly don't try to go down
to five or three or points something never. And again,
the reason for that is that the more vigorously you
treat these tumors and the farther you push them down,
(16:53):
the more rapidly you produce a treatment resistant tumor situation. Now,
having said that, you know, can we ever get to
a cure with this? And by cure I'm going to
define that as the disease goes away and never comes back.
There are some interesting findings from pilot studies at Moffitt
(17:16):
Cancer Center in Florida with prostate cancer patients. After five
to eight years, some of the patients started on an
adaptive protocol seemed to when they've been taken off there,
when they've been given a treatment holiday in the adaptive protocol,
sometimes the PSA has not risen again, it has stayed low,
(17:39):
and those patients may be cured. We don't know yet.
We have to you know, the data aren't mature. We
have to see what happens to those patients over many years.
But that was very encouraging and a surprise actually to
see that. Yes, perhaps in some cases this process led
to an even better outcome than we we thought it might.
Speaker 2 (18:04):
Yeah, it's just very interesting. It's so different than everything
else about oncology, which is, you know, of course, to
eradicate the tumor as quickly and as completely as possible.
Speaker 3 (18:16):
So how do you Well, I do want to say
that in a curative situation, that is exactly what you
want to do. So if the doctor, the oncologists again says,
you know, we can eradicate this tumor, then you do
want to hit it hard and fast and as you know,
as quickly and as thoroughly as possible. That's a different scenario.
So again, the adaptive approach would not be appropriate in
(18:38):
that kind of situation. MH.
Speaker 2 (18:41):
So, I think you've kind of touched on this, maybe
without using the terminology, but you talk about cellular senescence
and that being a predictor of treatment toxicity. So can
you talk a little bit about what that is and
how you use that to improve your outcomes and treatment tolerance.
Speaker 3 (18:58):
Sure, we don't know yet, So the research award that
my team was granted last month actually is going to
look into that. So we believe from animal studies that
cellular senescence can predict treatment toxicity. And what cellular senessence
(19:20):
is is the normal aging of cells. Happens with years.
It can also happen with exposure to toxins, radiation, things
like that. Anything that damages cellular DNA can lead to
what's called cellular sedesence, which is the arrest of the
growth cycle. So if a cell it has been damaged
(19:41):
beyond repair, it will never divide again. The division machinery
is blocked and turned off, and that cell may stay alive,
but it just sits there and doesn't reproduce. That may
be a good thing, we think in many cases. We
think that these are cells that might otherwise become cancers
because of the damage that they've entertained. But the problem
(20:06):
with SINESM cells is that they will also elaborate some
something called the sinesence associated They will put out cytokines
and inflammatory molecules that can affect surrounding tissues and maybe
even the whole body. So they're not a great It's
not a great thing to have a lot of sinessem
(20:28):
cells around if you kill off sinesm cells, and there
are medications and you know, certainly natural substances like physetin
and quersotin and some drugs that can kill off sinesm cells,
but if you do too much of that, you kind
of deplete your stem cell pool and so you may
have some frailty issues with that. So it's kind of
(20:50):
a dilemma. One of the things that we've found is
that sinessence, especially in blood cells, may predict an inability
to tolerate right high dose chemotherapy and other types of
therapy cancer therapy as well. So we're one of the
things that we're going to look at is is that true,
(21:10):
and how does that work? And can we predict based
on certain patterns of sin essence in cells whether we
might need to back off on, you know, certain types
of treatment in certain patients. It's hard to tell which
patients are going to you know, a lot of patients
do very very well with their very strong cancer UH medications.
(21:34):
Some patients, however, have really horrible problems side effects. If
we could predict ahead of time who those patients might be,
we can of course, modify their their treatment and also
be ready with treatments for the side effects a little
sooner than we might be otherwise.
Speaker 2 (21:55):
And your present is also about the role of the
gut microbiome, so this is a whole new l to
this and how does how do you incorporate the gut
microbiome into this modeling that you're using.
Speaker 3 (22:08):
Sure, so one of the things that we've gotten a
grant to study is how the gut microbiome changes with
chemotherapy in a very organized way, and that's not been done.
That kind of research hasn't been hasn't been done very much,
so we're really proud of that. It's it's a new
way to look at cancer and treatment toxicity. So we
(22:28):
do know that that cancer treatments affect the microbiome. We
are going to make an organized inquiry into how the
gut microbiome is damaged throughout the course of chemotherapy in
ovarian cancer specifically, and we hope that that information eventually
(22:51):
can be used to both predict and moderate chemotherapy toxicity
in those patients. And so we suspect we don't know
we're going to look into this. We suspect that if
we can keep the microbiome in good shape, and if
we figure out how to do that, we will be
able to make the cancer treatment work better. Otherwise, we
(23:13):
think patients will have a better chance of getting well
if we can keep their gut in good shape.
Speaker 2 (23:21):
Yes, indeed. Well, I'm wondering what you think is this
revolutionary stuff? I mean, is this going to completely change
the way that cancer care is delivered or is this
sort of something that you see is going to play
a role but maybe not really make it into the
big time.
Speaker 3 (23:42):
I think it's already in the big time, and I
think it will be very revolutionary. I think the idea
that we can improve the way we actually administer drugs
by changing the schedule is really is revolutionary. So there
are a lot of rhythms in nature, and so far
we've as a as a group I'm talking about doctors, uh,
(24:05):
medical oncologists, we've ignored those rhythms quite a bit. So
there are rhythms to the best times to give treatments,
there are rhythms to the best time to test and
inter act with the microbiome, those kinds of things, and
that's one of the things that we haven't been able
to look at until now when we have new ways
(24:28):
of looking at the gut metabolomics, proteomics, those things can
be checked frequently, and we are doing that now, and
we see these huge fluxes in the gut microbiome over
the course of you know, minutes and you know, certainly
(24:49):
hours and days. And we've looked at you know, microbiome
snapshots you know, maybe once or twice a year, and
we may sure not that we have to look several
times a day or something like that to really be
able to manipulate and take advantage of the rhythms there
for patient well being and healing.
Speaker 2 (25:11):
Mm So do you think adaptive therapy what will it
take to bring this adaptive therapy type of treatment to
patient care in most patient care centers, Because I mean,
I think it's it's available, but it's not easy to find.
Speaker 3 (25:29):
You know. I don't know of any place outside of
academia accept my practice that is actually actively doing this.
There may be other on coologists who are doing this privately,
but certainly larger academic centers are now taking a look
at it. I think Moffatt was one of the first
Arizona State University up the street is also one of
(25:53):
the leaders in evolutionary oncology. I'm a member of the
Americans as you for Cancer Research Working Group on Cancer Evolution,
and there are leaders from many wonderful institutions there who
are starting to take notice of this and working to
(26:17):
study it and to apply it to patient care. So
I do think, you know, in ten years, it will
be standard to use adaptive protocols in many of these cancers, okay,
And I think it will be standard to at least
look at the microbiome and attempt to intervene, you know,
(26:40):
when when it's damaged by treatment or just from life
or by the cancer itself.
Speaker 2 (26:45):
Right, Yeah, Okay, Well I'm gonna hold you to that.
So any last minute final thoughts you'd like to leave
with our listeners.
Speaker 3 (26:54):
Yeah. So, so, you know, there are some you know,
more it's not better in terms of advanced cancer treatment
and always, and I think that's something that needs to
be kind of shouted from the mountaintops that you know,
but just giving low dose there used to be something
(27:17):
called metronomic chemotherapy, which was basically giving a low dose
of chemotherapy and maybe giving it based on you know,
a calendar type of schedule like once a week or
you know, something like that. That doesn't work very well.
Either it worked every it worked occasionally, and that's why
it kept caught on. Every now and then a patient
would get better. And what the reason is is we've
(27:38):
found is that that's those are the patients whose tumors
accidentally matched the calendar. Most patients don't. Everybody's tumor has
a different growth rate. Tumor growth rates can change from
different seasons. They change across the course of the day.
For instance, tumors tend to grow faster at night. So
so all these things I think, uh, you know, I
(28:00):
want people to to to open their minds and understand that,
you know, the mathematics and cycles of nature play a
big role in all of nature, including cancer growth. And
as we unlock these, uh, the ways that these things work,
we can treat patients with a lot more skill.
Speaker 2 (28:22):
Amazing, Well, continue your good work, and how do our
listeners find you? Can you give us a website?
Speaker 3 (28:28):
So I have a website. It's called Oregon Integrative Oncology
and the u r L is based on that name,
and the u r L is Oregon like the state
O R E G O n IO dot com and
I also have a podcast called Docs Talk Shop and
(28:49):
you can listen to to that on any of the
major podcasts outlet and I do have some some episode
that go into detail on adaptive therapy.
Speaker 2 (29:03):
Great well, thank you so much, Don, It's really been
a pleasure talking with you. And keep up your good work.
I'll keep an eye on it for sure. And that
wraps up this episode of five to Thrive Live. We
thank our sponsors Cognizance of Cooline for memory, focus and attention,
Immuse post Biotic for immune support, Doctor Hires Probiotics award
(29:24):
winning pre and probiotic formulas and pro Thrivers wellness supplements
designed specifically for thrivers. May you experience joy, laughter and love.
It's time to thrive everyone, have a great night.
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