AACR 102nd Annual Meeting, 2—6 April 2011, Orlando, Florida

Effects of stress on cancer progression

Professor Anil Sood – MD Anderson Cancer Center, Houston, USA

It is generally agreed that stress is important in medical care and chronic stress is something you’ve been looking at, Anil Sood, at your session. You had a whole session with several speakers devoted to stress, what it does to the body, and that is biochemically. Now, can you tell me what came out of this, because you’ve been looking at the sort of pathways that go on that might be caused by stress and how they might influence disease processes?

Sure, I will discuss two or three highlights that came out of this session. One is that it has been known for a long time that chronic stress can affect many other processes within the body such as causing coronary heart disease, gastrointestinal disturbances and so on, so we always suspected that why wouldn’t it also affect cancer growth and progression. So some of the highlights that came out of this session were that even though it’s been now recognised that chronic stress plays a prominent role in cancer growth and progression, we don’t understand the mechanisms fully. So some of the mechanisms that were presented in this particular session were how chronic stress and related hormones can stimulate what’s called angiogenesis, or the blood supply to the tumours, which creates a net effect of increased tumour growth.

Where do things like the fight and flight response, noradrenalin or norepinephrine come into all of that?

A great point. Those kinds of hormones, what they do is they can stimulate these receptors directly on the cancer cells called beta-adrenergic receptors and this produces then high levels of growth factors such as vascular endothelial growth factor as well as many other factors that promote the blood supply to the tumours.

And glucocorticoids are relevant too, aren’t they?

Glucocorticoids are very important, they seem to have another role in terms of cancer biology. Glucocorticoids, such as cortisol, seem to protect cancer cells from the effects of chemotherapy, so chemotherapy doesn’t work as well when there are high levels of glucocorticoids around.

But there is acute stress, which is what Mother Nature wanted us to have for the fight and flight, but there’s also chronic stress, how do you distinguish between the two and what the consequences, in terms of cancer, might be?

Acute stress is very adaptive, it’s normal, it’s important for our daily function. So an example of acute stress would be doing what I did yesterday – getting in front of 200 people and giving a talk. That’s acute stress, your hormones will spike and then they will go back down quickly. But, just like with most things in life, if you do too much of something then it turns out to be not as good. Chronic stress is where there is no end in sight, so some examples would be caretakers of chronically ill people. So, for instance, a caretaker of an individual who has Alzheimer’s disease, or who has cancer, where they are going to live for a long time but the caretakers are some of the most stressed individuals in that regard. Other examples can also be major depression, loneliness, things like that, can also relate to some of the effects similar to chronic stress.

Now you particularly were talking about adrenergic regulation and the tumour microenvironment. What did you have to say about this?

What I had to say was that the microenvironment becomes really conditioned, or that chronic stress and related hormones really create a very permissive environment for tumour growth and invasion and spread to occur. If we use drugs that have been used for a long time for high blood pressure, such as beta blockers, those can block some of the adverse effects of chronic stress in the context of tumour growth.

And you heard also from another speaker that you can remove apoptosis, or inhibit it, as well which also might be of use?

That is correct. In that context, Dr Kulik studied prostate cancer where they found that some of the stress hormones can again protect cancer cells from the effects of other drugs, and if you use beta blockers in that context they can sensitise these tumours to the effects of chemotherapy and so on.

You had a talk about breast cancer, is there a link between stress and breast cancer? Over the years there have been quite a lot of studies on this, it’s always been quite difficult to prove, hasn’t it?

So the links between chronic stress and cancer initiation, or formation of cancer, that’s a very different question and those links have never been strong. But where there are strong links are the effects of chronic stress on tumour growth and progression, meaning the spread of cancer. So whether you look at breast cancer, whether you look at many other cancer types, those links are actually quite strong at this point.

Then beta adrenergic regulation of gene expression, that’s amazing.

What Dr Cole reported is that even in human ovarian cancers that come from individuals who are affected by chronic stress, that there is a very prominent gene signature that reflects inflammation. So it really is a very complete story that these are not just theoretical concepts but rather they manifest themselves directly in human tumour samples as well.

Coming out of this very rich session, rich informationally, what do you pull out of it in terms of hard data that you think cancer doctors, for example, could hang their hats on?

At this point a session like this really becomes very informative in the context of understanding mechanisms and coming up with even potentially important biomarkers for understanding the effects of stress. That’s where the field is at this point; the next steps are to continue to understand mechanisms and then, in the long run, to develop innovations to block some of the bad effects of chronic stress.

What are the main biomarkers that have come out so far, judging from your session?

Things like looking at cortisol levels, some of the flight or fight response hormones, also inflammation related genes all seem to be a part of chronic stress response.

Do you think there could be a benefit for clinicians in checking on some of these biomarkers?

Routinely at this point we think it’s a bit early and it would be premature to start to check these routinely because a lot of these studies are early at this point, they need to continue to be expanded, gain a better mechanistic understanding. And then in the long run we hope that we can identify a set of biomarkers and, very importantly, identify a set of interventions by which you could block some of these bad effects.

What, then, is the take home message from your session on stress and cancer?

The take home message is that it is becoming increasingly clear that chronic stress can have prominent effects in terms of cancer growth and progression and that the mechanisms are now starting to be elucidated and there are multiple mechanisms by which chronic stress affects cancer. And that the next steps in on-going research are fundamentally important in terms of making substantial gains in this field.

And you feel you actually can quantify it, you can define it and so you really can begin to understand the effects of stress?

Very much so. We feel that at this point it’s not just an abstract field but rather there are quantifiable parameters that can be used to make progress.

Dr Sood, thank you very much for joining us here on ecancer.tv.

Thank you for having me.