Promising New Tool in the Battle against Cancer-related Fatigue

Transcript

00:00 --> 00:02Funding for Yale Cancer Answers is
00:02 --> 00:04provided by Smilow Cancer Hospital.
00:06 --> 00:08Welcome to Yale Cancer Answers
00:08 --> 00:10with Doctor Anees Chagpar.
00:10 --> 00:12Yale Cancer Answers features the
00:12 --> 00:14latest information on cancer care
00:14 --> 00:15by welcoming oncologists and
00:15 --> 00:17specialists who are on the forefront
00:17 --> 00:19of the battle to fight cancer.
00:19 --> 00:21This week it's a conversation about
00:21 --> 00:23new research into cancer related
00:23 --> 00:25fatigue with Doctor Rachel Perry.
00:25 --> 00:27Doctor Perry is an assistant professor
00:27 --> 00:30of medicine in endocrinology and of
00:30 --> 00:31cellular and molecular Physiology
00:31 --> 00:33at the Yale School of Medicine,
00:33 --> 00:36where Doctor Chagpar is a professor
00:36 --> 00:37of surgical oncology.
00:37 --> 00:38Rachel,
00:38 --> 00:40maybe we'll start by you telling
00:40 --> 00:41us a little bit more about
00:41 --> 00:43yourself and what you do.
00:44 --> 00:46Absolutely. So I am a
00:46 --> 00:48metabolism trained scientist.
00:48 --> 00:50So I grew up as a scientist
00:50 --> 00:51studying metabolism.
00:51 --> 00:54That is how our bodies use nutrients
00:54 --> 00:57that we either take in from food or
00:57 --> 00:59generate in our bodies themselves
00:59 --> 01:02and where those nutrients go
01:02 --> 01:04and how those nutrients can be
01:04 --> 01:06used to either fuel tumor growth,
01:06 --> 01:07which is obviously a problem,
01:07 --> 01:10or to help our bodies fight tumor growth
01:10 --> 01:13and recover from having cancer.
01:13 --> 01:14So as I said,
01:14 --> 01:16my training was in pure metabolism,
01:16 --> 01:18just kind of looking at where
01:18 --> 01:19nutrients go and how they're
01:19 --> 01:20regulated throughout our body.
01:20 --> 01:23But when I started my lab in 2018,
01:23 --> 01:25I was really excited about getting
01:25 --> 01:27into the intersection between
01:27 --> 01:29metabolism and cancer because
01:29 --> 01:31there's been a lot of interest in
01:31 --> 01:33cancer metabolism in recent years.
01:33 --> 01:35And I thought that there was
01:35 --> 01:37really a place for metabolism
01:37 --> 01:39focused scientists to apply
01:39 --> 01:43the tools and sort of ways that we
01:43 --> 01:45think about science to really
01:45 --> 01:47try to make a difference again in
01:47 --> 01:50terms of coming up with metabolism
01:50 --> 01:52targeting therapies and potentially
01:52 --> 01:54dietary and other recommendations for
01:54 --> 01:56patients who are dealing with cancer.
01:58 --> 02:00So let's take a a step back.
02:00 --> 02:02You know, I think when many
02:02 --> 02:05of us think about metabolism,
02:05 --> 02:07we we think about
02:07 --> 02:09diet and exercise and
02:09 --> 02:12revving up our metabolism to
02:12 --> 02:14burn off a few extra calories,
02:14 --> 02:16building muscle that builds your
02:16 --> 02:18metabolism and that kind of thing.
02:18 --> 02:21Can you talk a little bit more about
02:21 --> 02:24what exactly is metabolism and what is
02:24 --> 02:27the Nexus between metabolism and cancer?
02:28 --> 02:30Sure. So metabolism is
02:30 --> 02:33really the study of what's coming in
02:33 --> 02:35and what's going out as far as nutrition,
02:36 --> 02:37as far as nutrients.
02:37 --> 02:40So what comes in boils down to
02:40 --> 02:42both the foods that we eat as well
02:42 --> 02:44as what our body does itself.
02:44 --> 02:46So many people aren't aware that
02:46 --> 02:49our bodies do quite a bit in
02:49 --> 02:50terms of generating metabolites.
02:50 --> 02:54So that is generating nutrients and then
02:54 --> 02:57using those nutrients in various pathways.
02:57 --> 02:59And there are a lot of places
02:59 --> 03:01that we can intervene in that process
03:01 --> 03:04and change what nutrients our
03:04 --> 03:06bodies are generating in a way that
03:06 --> 03:08could potentially be beneficial.
03:08 --> 03:08And in addition,
03:08 --> 03:10I mentioned it's the study of what's
03:10 --> 03:11coming in and what's going out.
03:11 --> 03:13What's going out is where
03:13 --> 03:15those nutrients are going.
03:15 --> 03:16So for instance,
03:16 --> 03:18if our liver makes glucose,
03:18 --> 03:21so that's sugar that our liver can make when
03:21 --> 03:23we haven't had anything to eat in a while,
03:23 --> 03:25where does that sugar go?
03:25 --> 03:26Does it go to our muscle?
03:26 --> 03:27Does it go to our brain?
03:27 --> 03:28If we have cancer,
03:28 --> 03:30does it go to our tumor?
03:30 --> 03:32And how can we intervene to send those
03:32 --> 03:34nutrients to a place where they're
03:34 --> 03:36more beneficial like to our brain or
03:36 --> 03:38to our heart as opposed to somewhere
03:38 --> 03:40where they would cause us a problem,
03:40 --> 03:41for instance,
03:41 --> 03:42going to a tumor.
03:42 --> 03:45And when you ask about the intersection
03:45 --> 03:47between metabolism and cancer,
03:47 --> 03:48this is really,
03:48 --> 03:50I wouldn't say an open question,
03:50 --> 03:54but an an area of a lot of active study.
03:54 --> 03:57So there's been for the last 100 years a
03:57 --> 04:00knowledge that tumors really like glucose.
04:00 --> 04:03So tumors take sugar and this
04:03 --> 04:05fuels tumor growth quite a bit.
04:05 --> 04:07But what we've learned in recent years
04:07 --> 04:10through work from our lab as well
04:10 --> 04:12as many other wonderful labs is that
04:12 --> 04:15there this is a lot more nuanced than
04:15 --> 04:18simply glucose fuels tumor growth.
04:18 --> 04:19So number one,
04:19 --> 04:21there are various nutrients
04:21 --> 04:23that are fuels for immune cells.
04:23 --> 04:25We know that our immune cells are
04:25 --> 04:27quite important in the anti cancer
04:27 --> 04:29response and immune cells like glucose,
04:29 --> 04:32they like amino acids and potentially
04:32 --> 04:33there are additional
04:33 --> 04:35mechanisms of metabolic regulation
04:35 --> 04:38of the immune response to cancer.
04:38 --> 04:39And in addition,
04:39 --> 04:41it's not just glucose for tumors.
04:41 --> 04:44So tumors are really good at
04:44 --> 04:45using whatever metabolites,
04:45 --> 04:47whatever nutrients we provide to them.
04:47 --> 04:52And so in my view being able to
04:52 --> 04:54intervene effectively in this
04:54 --> 04:55intersection between metabolism
04:55 --> 04:58and cancer is really going to
04:58 --> 04:59require thoughtful approaches that
04:59 --> 05:01combine metabolic interventions with
05:01 --> 05:03additional anti cancer interventions
05:03 --> 05:07so that we can potentially boost the
05:07 --> 05:09effectiveness of anti cancer treatments
05:09 --> 05:11like chemotherapy and immunotherapy.
05:12 --> 05:15You know, when you talk about
05:15 --> 05:17tumor cells being fed by
05:17 --> 05:19metabolites like glucose or sugar,
05:19 --> 05:22this brings up one of the
05:22 --> 05:25common questions that we get asked,
05:25 --> 05:28which is if you've been diagnosed
05:28 --> 05:32with cancer and cancer feeds on sugar,
05:32 --> 05:34should you cut out all sugar from your
05:34 --> 05:37diet in order to starve cancer cells?
05:38 --> 05:40Well, I think my first response is that,
05:40 --> 05:43you know, we can never blame patients
05:43 --> 05:45for having done the wrong thing
05:45 --> 05:48from a dietary standpoint or a
05:48 --> 05:51lifestyle standpoint in any way because
05:51 --> 05:53there's no way to predict that
05:53 --> 05:55one will eventually develop cancer.
05:55 --> 05:57And in addition, if one were to have
05:57 --> 05:59cancer and completely cut out sugar,
05:59 --> 06:01unfortunately there's no guarantee
06:01 --> 06:03that will have a beneficial
06:03 --> 06:05effect on their prognosis.
06:05 --> 06:06But that said,
06:06 --> 06:08there is literature that reducing sugar
06:08 --> 06:11one doesn't have to cut it out completely,
06:11 --> 06:13but really reducing sugar
06:13 --> 06:15and consuming a high protein,
06:15 --> 06:18high fat diet that is low in
06:18 --> 06:19sugar may have beneficial effects
06:19 --> 06:22in a number of types of cancer.
06:22 --> 06:25And there is ongoing research,
06:25 --> 06:28this isn't a sort of conclusive study yet,
06:28 --> 06:30but there is quite a bit of
06:30 --> 06:32evidence from both animal models
06:32 --> 06:35and also human clinical trials
06:35 --> 06:36that reducing sugar, lowering
06:36 --> 06:39the carbohydrates in our diet, may
06:39 --> 06:41have beneficial effects on cancer.
06:42 --> 06:46OK. But just to kind of delve into
06:46 --> 06:50that just a tad more because that brings
06:50 --> 06:52up a couple of other key questions.
06:52 --> 06:56One is that people will say, I'm going
06:56 --> 06:59to avoid eating fruits and vegetables,
06:59 --> 07:03especially fruit because fruit has sugar.
07:03 --> 07:05What do you think about that?
07:05 --> 07:07Many nutritionists will say to a
07:07 --> 07:10cancer patients that they should
07:10 --> 07:13eat a predominantly plant based
07:13 --> 07:15diet with fruits and vegetables.
07:15 --> 07:18But if fruits have sugar and
07:18 --> 07:19sugar feeds cancer,
07:19 --> 07:20isn't that a disconnect?
07:21 --> 07:23So that's a great question and
07:23 --> 07:25the answer really is that there
07:25 --> 07:26are different types of sugar.
07:26 --> 07:28So evidence has shown that
07:28 --> 07:31the worst type of sugar to consume in
07:31 --> 07:34general for our health as well in cancer
07:34 --> 07:37is what's called high fructose corn syrup.
07:37 --> 07:40And so this is added sugar that's in,
07:40 --> 07:43you know, cereals and cake and
07:43 --> 07:45cookies and things like that.
07:45 --> 07:49The sugar that's in that high
07:49 --> 07:52fructose corn syrup causes a host of
07:52 --> 07:54metabolic problems and it seems to
07:54 --> 07:56be more efficient at fueling tumor
07:56 --> 07:58growth than other types of sugars.
07:58 --> 08:00The sugar that is in fruit is
08:00 --> 08:02sort of a more quote UN quote,
08:02 --> 08:04natural sugar that has less of
08:04 --> 08:06a detrimental effect when it
08:06 --> 08:08comes to fueling cancer growth.
08:08 --> 08:11But that said, the
08:11 --> 08:13evidence would suggest that it is
08:13 --> 08:16absolutely fine to consume sugar and
08:16 --> 08:17absolutely healthier to consume,
08:17 --> 08:20sorry, absolutely fine to consume fruit.
08:20 --> 08:22I didn't mean to say sugar,
08:22 --> 08:25absolutely fine to consume fruit and better
08:25 --> 08:28to use fruit rather than for instance,
08:28 --> 08:31cake if we want to satisfy our sweet tooth.
08:31 --> 08:32But you know,
08:32 --> 08:34it's probably a good idea for cancer
08:35 --> 08:37patients to try to some degree
08:37 --> 08:39limit the amount of fruit intake as
08:39 --> 08:41well because it does have some
08:41 --> 08:43degree of sugar that can be broken
08:43 --> 08:46down and metabolized in a way that
08:46 --> 08:48could potentially fuel tumor growth.
08:48 --> 08:50But with all that said, you know,
08:50 --> 08:52dietary recommendations have to
08:52 --> 08:53be what we call palatable.
08:53 --> 08:55They have to be doable for the patient.
08:56 --> 08:58I think it's much better,
08:58 --> 09:01per what all the research says,
09:01 --> 09:04to consume a little bit of fruit
09:04 --> 09:06amidst a high protein diet that you
09:06 --> 09:09can actually stick to rather than
09:10 --> 09:13making no dietary modifications at all.
09:13 --> 09:15And if that fruit makes the
09:15 --> 09:16diet more palatable,
09:16 --> 09:18it's absolutely worth it.
09:18 --> 09:21Then the final question on
09:21 --> 09:23this kind of line is, you know,
09:23 --> 09:25if we're trying to avoid sugar
09:25 --> 09:26but we still have a sweet tooth,
09:27 --> 09:30what are the current thoughts
09:30 --> 09:31about artificial sweeteners?
09:31 --> 09:34We've seen that, you know,
09:34 --> 09:36some organizations have said
09:36 --> 09:38that artificial sweeteners
09:38 --> 09:40might actually be carcinogenic,
09:40 --> 09:43but if sugar also fuels cancer,
09:43 --> 09:45then isn't that carcinogenic
09:45 --> 09:48too and if so, which is worse?
09:49 --> 09:52Absolutely. And so to my knowledge,
09:52 --> 09:55most if not all of the research on artificial
09:55 --> 09:57sweeteners and cancer has been in vitro.
09:57 --> 10:00That means in cells in a dish where
10:00 --> 10:03in most cases people are giving
10:03 --> 10:05very very high concentrations of
10:05 --> 10:07the artificial sweeteners.
10:07 --> 10:10And it turns out that if you
10:10 --> 10:12give high concentrations of many
10:12 --> 10:14different chemicals to cells,
10:14 --> 10:16this can have an effect to
10:16 --> 10:18promote cancer, again in a dish.
10:18 --> 10:21I'm not aware of convincing
10:21 --> 10:23clinical trials in people that
10:23 --> 10:27control for other relevant factors.
10:27 --> 10:28So for instance,
10:28 --> 10:30many times people may be shifting
10:30 --> 10:32to using artificial sweeteners
10:32 --> 10:34in an attempt to lose weight.
10:34 --> 10:37So these for instance may be people
10:37 --> 10:40who have obesity at baseline or who
10:40 --> 10:42have metabolic dysfunction at baseline.
10:42 --> 10:44And then you sort of can't de convolve
10:44 --> 10:46the effects of the artificial sweeteners
10:46 --> 10:49from the effects of the underlying
10:49 --> 10:50problems with metabolic health.
10:50 --> 10:53So personally I would say if
10:53 --> 10:55my family or friends ask
10:55 --> 10:56me for a recommendation,
10:56 --> 10:59although I'm not a doctor and so I
10:59 --> 11:01can't give clinical recommendations,
11:01 --> 11:03but I would say absolutely
11:03 --> 11:06artificial sweeteners would be
11:06 --> 11:09expected to be better in terms of
11:10 --> 11:12lowering the cancer risk when substituting
11:12 --> 11:15for sugar as opposed to sugar.
11:15 --> 11:17And frankly for myself that
11:17 --> 11:19is what I do, using artificial
11:19 --> 11:21sweeteners rather than sugar.
11:21 --> 11:23Phew, because that's what I do too,
11:24 --> 11:26full disclosure. So I want
11:26 --> 11:29to now kind of move into the
11:29 --> 11:31work in your lab
11:31 --> 11:35looking at how you can kind
11:35 --> 11:37of target these metabolic
11:37 --> 11:40pathways in terms of cancer.
11:40 --> 11:41Can you talk a little bit
11:41 --> 11:42more about your research?
11:43 --> 11:44Absolutely. So because of
11:44 --> 11:46my background in metabolism,
11:46 --> 11:49we've been applying a number of
11:49 --> 11:51different metabolism targeting drugs
11:51 --> 11:55in mouse cancer models and sort
11:55 --> 11:57of tracing what they do to the response
11:57 --> 11:59to immunotherapy and chemotherapy
11:59 --> 12:02and tumor growth by itself.
12:02 --> 12:04And so there have been several
12:04 --> 12:05recent studies,
12:05 --> 12:07one of which was looking at trying to
12:07 --> 12:09develop a precision medicine approach,
12:09 --> 12:13so using tumor genetics to predict
12:13 --> 12:16response and applying a common diabetes
12:16 --> 12:19drug that's called an SGLT 2 inhibitor.
12:19 --> 12:21And we showed that you can predict
12:21 --> 12:23which tumors may be more likely to
12:23 --> 12:25respond to the SGLT 2 inhibitor than
12:25 --> 12:27others based on the tumor genetics.
12:27 --> 12:29And I think that's very important
12:29 --> 12:30because a lot of,
12:30 --> 12:33well really all of the metabolism
12:33 --> 12:35targeting human clinical trials
12:35 --> 12:37that have been done have not
12:37 --> 12:39been based on tumor genetics.
12:39 --> 12:40We're using precision medicine
12:40 --> 12:42for everything else in oncology,
12:42 --> 12:43not everything else,
12:43 --> 12:45but almost everything else.
12:45 --> 12:46And so I think there's really
12:46 --> 12:48a role for precision medicine,
12:48 --> 12:49metabolic therapy.
12:49 --> 12:51And with that
12:51 --> 12:54there are also sort of unexpected
12:54 --> 12:56findings that can come out.
12:56 --> 12:59We had a recent paper that just came
12:59 --> 13:02out showing a metabolism targeting
13:04 --> 13:07modality for cancer related fatigue.
13:07 --> 13:09And so it's been a lot of fun
13:09 --> 13:12in recent years to look at what
13:12 --> 13:14metabolism targeting agents do and
13:14 --> 13:17how we can use them not only as anti
13:17 --> 13:19tumor agents but also
13:19 --> 13:22to reduce the complications of
13:22 --> 13:23cancer itself and cancer therapy.
13:24 --> 13:27So we're going to pick up that
13:27 --> 13:29conversation right after we take a
13:29 --> 13:30short break for a medical minute.
13:30 --> 13:33Please stay tuned to learn more about
13:33 --> 13:34battling cancer related fatigue
13:34 --> 13:36with my guest, Doctor Rachel Perry.
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14:54 --> 14:57You're listening to Connecticut Public Radio.
14:57 --> 14:57Welcome
14:57 --> 14:59back to Yale Cancer Answers.
14:59 --> 15:00This is Doctor Anees Chagpar
15:00 --> 15:02and I'm joined tonight by my guest,
15:02 --> 15:04Doctor Rachel Perry.
15:04 --> 15:06We're discussing the use of a new drug
15:06 --> 15:08to battle cancer related fatigue.
15:08 --> 15:11Now we really didn't get into the drug
15:11 --> 15:15itself because right before the break,
15:15 --> 15:17Rachel was telling us more about
15:17 --> 15:20some of the work that her lab does
15:20 --> 15:22in looking at metabolism and cancer.
15:22 --> 15:25So Rachel, can you kind of pick up
15:25 --> 15:27the conversation from where we were?
15:27 --> 15:30So my understanding is that you're
15:30 --> 15:34now looking at using more precision
15:34 --> 15:39genetics and genomics to look at
15:39 --> 15:41metabolism both for therapeutics
15:41 --> 15:45as well as to to battle fatigue.
15:45 --> 15:47So can you talk a little bit more
15:47 --> 15:49about how exactly that works and
15:49 --> 15:51and what your findings have been?
15:51 --> 15:54Based on the literature we had a
15:54 --> 15:57suspicion that increasing whole body and
15:57 --> 16:00specifically immune cell glucose metabolism,
16:00 --> 16:02so sugar metabolism specifically may improve
16:02 --> 16:05the response to immunotherapy and cancer.
16:05 --> 16:07So we thought that by giving a
16:07 --> 16:10drug to Rev up glucose oxidation,
16:10 --> 16:13so glucose metabolism, that this may
16:13 --> 16:15improve the response to immunotherapy
16:15 --> 16:17against Melanoma in mouse models.
16:17 --> 16:19So skin cancer in mouse models,
16:19 --> 16:20and we treat it with with the help
16:20 --> 16:22of a wonderful graduate student,
16:22 --> 16:25who is defending her PhD
16:25 --> 16:28soon and moving on to the next steps.
16:28 --> 16:31She treated a number of mice with Melanoma
16:31 --> 16:33with a drug called dichloroacetate,
16:33 --> 16:36and I'll refer to it as DCA in this
16:36 --> 16:38talk because it's much quicker.
16:38 --> 16:41And so when she treated mice with DCA,
16:41 --> 16:43we were expecting to see that it would
16:43 --> 16:44improve the response to immunotherapy.
16:44 --> 16:47But that did not turn out to be the case.
16:48 --> 16:50We studied a number of mice,
16:50 --> 16:51very careful experiments.
16:51 --> 16:53It did not improve the response
16:53 --> 16:54to immunotherapy,
16:54 --> 16:56but we were very pleasantly surprised and
16:56 --> 16:59excited to see that there was a phenotype.
16:59 --> 17:02So DCA made the mice a lot more
17:02 --> 17:05quote UN quote perky. The mice,
17:05 --> 17:06despite having large tumors,
17:06 --> 17:08moved around their cage.
17:08 --> 17:09They were, you know,
17:09 --> 17:11mice will climb the walls of their cage,
17:11 --> 17:13grab the top of their cage and climb
17:13 --> 17:15on top of it if they're healthy,
17:15 --> 17:17but not when they have a large tumor.
17:17 --> 17:19But these mice treated with DCA,
17:19 --> 17:21their physical performance was
17:21 --> 17:23completely preserved despite having
17:23 --> 17:26fairly large tumors at this stage.
17:26 --> 17:27And we thought,
17:27 --> 17:27you know,
17:27 --> 17:29we're not mouse behavioralists,
17:29 --> 17:32but this is a clear effect.
17:32 --> 17:34And so that really brought us into
17:34 --> 17:36the world of cancer related fatigue.
17:36 --> 17:38It's one of these happy accidents
17:38 --> 17:40sometimes in science,
17:40 --> 17:41you can do the good science,
17:41 --> 17:42you can have the good plan,
17:42 --> 17:44but it may not turn out the way
17:44 --> 17:46you're expecting because really
17:46 --> 17:47if we already knew the answer,
17:47 --> 17:49we wouldn't be doing the experiment.
17:49 --> 17:51And this was one of these wonderful
17:51 --> 17:53cases where although the initial
17:53 --> 17:54result was disappointing,
17:54 --> 17:57DCA did not slow tumor growth,
17:57 --> 17:59we ended up having a really exciting
17:59 --> 18:01finding that that DCA could improve
18:01 --> 18:03cancer related fatigue in mice.
18:03 --> 18:05Part of that makes me
18:05 --> 18:08wonder if DCA was the idea behind it.
18:08 --> 18:11And correct me if I've misunderstood,
18:11 --> 18:13if the idea behind it was to Rev up
18:13 --> 18:15the metabolism so that they would
18:15 --> 18:17respond better to immunotherapy,
18:17 --> 18:19it sounds like it revved up
18:19 --> 18:21their metabolism to
18:21 --> 18:22run around their cages,
18:22 --> 18:24but really didn't Rev up their
18:24 --> 18:27metabolism to respond to the therapy.
18:27 --> 18:29Why the disconnect?
18:29 --> 18:32It's an open question certainly and
18:32 --> 18:34I don't have a conclusive answer,
18:34 --> 18:37there have been studies using higher doses
18:37 --> 18:40of DCA that do show beneficial effects.
18:40 --> 18:44So I think it may be a dosing question,
18:44 --> 18:47but we sort of come at it from the angle
18:47 --> 18:49of it was disappointing that it
18:49 --> 18:51didn't improve the response to immunotherapy,
18:51 --> 18:53but if it makes the mice feel better,
18:53 --> 18:55so down the road if it makes the
18:55 --> 18:56patients feel better, that
18:56 --> 18:58could still be a beneficial effect.
18:58 --> 19:01And honestly there is literature in from
19:01 --> 19:03human patients showing that patients
19:03 --> 19:05who undergo cancer related fatigue,
19:05 --> 19:08which is a severe debilitating fatigue
19:08 --> 19:11that can't be relieved with sleep,
19:11 --> 19:13unlike the fatigue that we might
19:13 --> 19:15feel if we're running a marathon.
19:15 --> 19:17Having cancer related fatigue actually
19:17 --> 19:20reduces the likelihood that patients will
19:20 --> 19:22fully complete their cancer treatment.
19:22 --> 19:24There are patients who feel so crummy
19:24 --> 19:26because of cancer related fatigue
19:26 --> 19:28that they actually don't take their
19:28 --> 19:30treatment to completion and
19:30 --> 19:32that not completing cancer treatment
19:32 --> 19:34would obviously be expected to have
19:34 --> 19:37detrimental effects on cancer outcomes.
19:37 --> 19:39So I think although you know mice don't
19:39 --> 19:41get to choose whether or not
19:41 --> 19:43they complete their cancer treatment.
19:43 --> 19:46I think down the road if this were
19:46 --> 19:47to move to human patients,
19:47 --> 19:50there is the possibility that there could
19:50 --> 19:52in addition to improving quality of life,
19:52 --> 19:55there could be an effect to improve the
19:55 --> 19:58treatment success rates in patients.
19:59 --> 20:00I think that it's
20:00 --> 20:03really exciting. Has there
20:03 --> 20:06been movement beyond mice?
20:06 --> 20:08We would love to do that.
20:08 --> 20:10There hasn't been yet but there are some
20:10 --> 20:12hints that this may be possible.
20:12 --> 20:15So DCA actually was approved by the
20:15 --> 20:17FDA for treatment of another condition
20:17 --> 20:20called lactic acidosis and this is
20:20 --> 20:23the build up of lactate in the blood
20:23 --> 20:26and can happen for various reasons,
20:26 --> 20:28not necessarily related to cancer.
20:28 --> 20:30But actually in the 1980s DCA was
20:30 --> 20:33approved as a treatment for this disease.
20:33 --> 20:37And that is because DCA pulls carbon,
20:37 --> 20:40it pulls metabolites from
20:40 --> 20:43lactate and pyruvate which exchanges
20:43 --> 20:46with lactate into the DCA cycle.
20:46 --> 20:48And so it essentially depletes
20:48 --> 20:51the build up of lactate in the blood
20:51 --> 20:54and allows the body to oxidize it.
20:54 --> 20:56So using that fuel rather than
20:56 --> 20:57allowing it to build up.
20:57 --> 21:01And so because of that DCA as I
21:01 --> 21:03said was approved in the 1980s.
21:03 --> 21:05And so although it's not current
21:05 --> 21:07treatment in the hospital for
21:07 --> 21:09lactic acidosis because we have
21:09 --> 21:11better therapeutic approaches now,
21:11 --> 21:13the fact that it was FDA approved
21:13 --> 21:16indicates that it is safe and it
21:16 --> 21:17is effective at lowering lactate.
21:17 --> 21:20And so at this point we
21:20 --> 21:22are talking with colleagues and
21:22 --> 21:24thinking about potential next steps
21:24 --> 21:26toward a clinical trial using DCA
21:26 --> 21:28for cancer related fatigue because
21:28 --> 21:30we already know that it's safe and
21:30 --> 21:32effective at lowering lactate.
21:32 --> 21:35And related to that point I
21:35 --> 21:37do want to make it clear that at this stage
21:37 --> 21:39we really have no pharmaceutical
21:39 --> 21:41treatments for the entire syndrome
21:41 --> 21:43of cancer related fatigue.
21:43 --> 21:46So at this point
21:46 --> 21:48it's treated symptomatically so
21:48 --> 21:50inflammation can be treated with
21:50 --> 21:52ibuprofen drugs like that
21:53 --> 21:54if there are mental health symptoms
21:54 --> 21:57they can be treated with anti anxiety
21:57 --> 21:59or anti depression medications.
21:59 --> 22:02We may recommend yoga or you
22:02 --> 22:04know interventions like that.
22:04 --> 22:07But there really is no drug treatment
22:07 --> 22:09for the entire syndrome and we think
22:09 --> 22:12based on the mouse findings
22:12 --> 22:14that there is the possibility that
22:14 --> 22:16the DCA could potentially represent
22:16 --> 22:18the first pharmaceutical treatment for
22:18 --> 22:21the entire cancer related fatigue syndrome.
22:21 --> 22:22So that's really,
22:22 --> 22:23really exciting.
22:24 --> 22:25Tell us a little bit more about
22:25 --> 22:27some of the other work
22:27 --> 22:29you've been doing as well,
22:37 --> 22:40looking at metabolic interventions actually affect
22:40 --> 22:42effectiveness of treatment as well?
22:42 --> 22:44Yeah, absolutely. So you know,
22:44 --> 22:47both immune cells and tumor cells
22:47 --> 22:49need metabolites and so
22:49 --> 22:52there's a lot that we can do
22:52 --> 22:53potentially targeting systemic metabolism
22:53 --> 22:56to affect the efficacy of treatment.
22:56 --> 22:58So another ongoing study that we
22:58 --> 23:01have in the lab is to look at how
23:01 --> 23:03exercise actually seems to improve
23:03 --> 23:05outcomes in mice with breast cancer.
23:05 --> 23:08So we found that exercise,
23:08 --> 23:11running on the treadmill,
23:11 --> 23:13both slows tumor growth by itself
23:13 --> 23:15and also improves the effectiveness
23:15 --> 23:17of immunotherapy against triple
23:17 --> 23:18negative breast cancer.
23:18 --> 23:20And these are unpublished studies,
23:20 --> 23:23but it's an ongoing project in the lab.
23:23 --> 23:25And this is very exciting in
23:25 --> 23:27particular because with this project
23:27 --> 23:30we're looking to try to figure out
23:30 --> 23:32the mechanism by which this works.
23:32 --> 23:34So it's been shown multiple
23:34 --> 23:36times by many groups that exercise
23:36 --> 23:37slows cancer growth.
23:37 --> 23:40But we really don't know whether this
23:40 --> 23:43is through effects on tumor metabolism,
23:43 --> 23:46on immune cell metabolism or the interplay
23:46 --> 23:49between tumors and immune cells.
23:49 --> 23:51And our hypothesis, although we're
23:51 --> 23:53still working on it is that it's
23:53 --> 23:56really working by improving immune
23:56 --> 23:59cell efficacy against the tumors.
23:59 --> 24:01And the reason that this is
24:01 --> 24:03very important is that
24:03 --> 24:05cancer treatment is tough as you
24:05 --> 24:07know very well and not everybody
24:07 --> 24:08is able to exercise.
24:08 --> 24:11But if we can figure out the mechanism
24:11 --> 24:14by which exercise improves outcomes,
24:14 --> 24:16then there's the potential for developing
24:16 --> 24:18quote UN quote an exercise pill,
24:18 --> 24:21some sort of pharmaceutical intervention
24:21 --> 24:24that would recapitulate the effects
24:24 --> 24:26of exercise without actually forcing
24:26 --> 24:29people to do that exercise itself.
24:30 --> 24:34I mean certainly I think that where
24:34 --> 24:38possible exercise has a number of other
24:38 --> 24:40benefits in terms of cardiovascular
24:40 --> 24:44disease and other things.
24:44 --> 24:46Whether it's your
24:46 --> 24:48psychological well-being,
24:48 --> 24:50your cardiovascular fitness,
24:50 --> 24:51your gut motility,
24:51 --> 24:54not to mention your cancer. So
24:54 --> 24:57where possible it would be wonderful for
24:57 --> 25:01people to exercise and it's
25:01 --> 25:03wonderful that your research
25:03 --> 25:05has shown that that's beneficial.
25:05 --> 25:06It's certainly cost effective,
25:06 --> 25:08but you're quite right.
25:08 --> 25:09For people who can't,
25:09 --> 25:11the idea of an exercise
25:11 --> 25:13pill would be phenomenal.
25:14 --> 25:19Kind of tying that back to the DCA story,
25:19 --> 25:21have you found on a
25:21 --> 25:23molecular level that
25:23 --> 25:26the impact of DCA is similar to
25:26 --> 25:28exercise or are you thinking
25:28 --> 25:31that the exercise pill might
25:31 --> 25:33be something other than DCA?
25:33 --> 25:35So it sort of depends
25:35 --> 25:36on where we're looking at it.
25:36 --> 25:40So we find that from a cardio
25:40 --> 25:42metabolic health standpoint,
25:42 --> 25:44DCA is similar to exercise.
25:44 --> 25:46So DCA increases activity,
25:46 --> 25:48it increases muscular strength and
25:48 --> 25:51it also increases motivation very
25:51 --> 25:54similar to what exercise will do,
25:54 --> 25:57but that's a whole body level
25:57 --> 25:58and frankly that's very beneficial.
25:58 --> 26:01So cancer survivors unfortunately are at an
26:01 --> 26:03increased risk of cardiovascular disease,
26:03 --> 26:06so heart disease even after they
26:06 --> 26:08survive their cancer and
26:08 --> 26:09they finish their treatments.
26:09 --> 26:11We're still working on why this is,
26:11 --> 26:14but it is a very clear signal
26:14 --> 26:17and you know exercise is certainly a
26:17 --> 26:19potential intervention that can
26:19 --> 26:21help these survivors to reduce
26:21 --> 26:23that additional cardiovascular risk.
26:23 --> 26:25It seems that DCA may actually have
26:25 --> 26:26similar effects to potentially
26:26 --> 26:28and this is still ongoing work,
26:28 --> 26:32but the data would predict that DCA may
26:32 --> 26:34have similar effects to also reduce
26:34 --> 26:36that increased cardiovascular risk.
26:36 --> 26:39But if we're asking about the
26:39 --> 26:42effects of DCA on a molecular
26:42 --> 26:43level on the tumor itself,
26:43 --> 26:45it appears not to have those same
26:45 --> 26:47metabolic effects at the doses
26:47 --> 26:48that we treat people and
26:48 --> 26:50that we would treat animals with.
26:50 --> 26:52So I guess the question
26:52 --> 26:54as is often the case in science,
26:54 --> 26:57the question is really what is our question.
26:57 --> 26:59And so if we're targeting cancer related
26:59 --> 27:01fatigue and cardio metabolic health,
27:01 --> 27:02then absolutely.
27:02 --> 27:05If we're targeting the tumor itself,
27:05 --> 27:06maybe not.
27:08 --> 27:11So in our last minute or two,
27:11 --> 27:14it sounds like there's a lot of
27:14 --> 27:16really exciting things on the horizon.
27:16 --> 27:18What are you most excited about in
27:18 --> 27:20terms of future directions for your lab?
27:20 --> 27:22So many things, and
27:25 --> 27:26I love science more than anything.
27:27 --> 27:28And there's so
27:28 --> 27:29many exciting directions.
27:29 --> 27:31I think you know bringing these
27:31 --> 27:33studies into people and talking
27:33 --> 27:35with colleagues about potential
27:35 --> 27:36next steps to actually translate
27:36 --> 27:38this to the clinic would have
27:38 --> 27:40to be the most exciting thing.
27:40 --> 27:42We actually have a clinical trial
27:42 --> 27:44that's starting up very soon with
27:44 --> 27:46another metabolism targeting drug.
27:46 --> 27:48We don't have time to talk about
27:48 --> 27:49that today it seems.
27:49 --> 27:52But there are a lot of
27:52 --> 27:54clear translational opportunities.
27:54 --> 27:56And frankly this is particularly
27:56 --> 27:58exciting in the context of cancer
27:58 --> 28:00because these metabolism interventions
28:00 --> 28:02that we're talking about are so safe,
28:02 --> 28:05they are safe in healthy people,
28:05 --> 28:08in people with metabolic disease,
28:08 --> 28:10much more so frankly than a lot of
28:10 --> 28:12the approaches we use to treat cancer.
28:12 --> 28:15And so it seems like there's a large
28:15 --> 28:18amount of opportunity to really be
28:18 --> 28:20able to develop metabolism targeting
28:20 --> 28:23interventions that can help both cancer,
28:25 --> 28:27to slow tumor growth, and also really
28:27 --> 28:29improve quality of life.
28:29 --> 28:31Doctor Rachel Perry is an assistant
28:31 --> 28:33professor of medicine and endocrinology
28:33 --> 28:36and of cellular and molecular Physiology
28:36 --> 28:38at the Yale School of Medicine.
28:38 --> 28:40If you have questions,
28:40 --> 28:42the address is canceranswers@yale.edu,
28:42 --> 28:45and past editions of the program
28:45 --> 28:47are available in audio and written
28:47 --> 28:48form at yalecancercenter.org.
28:48 --> 28:51We hope you'll join us next week to
28:51 --> 28:53learn more about the fight against
28:53 --> 28:54cancer here on Connecticut Public Radio.
28:54 --> 28:57Funding for Yale Cancer Answers is
28:57 --> 29:00provided by Smilow Cancer Hospital.

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Promising New Tool in the Battle against Cancer-related Fatigue with guest Dr. Rachel Perry January 14, 2024