Cancer-related
fatigue (CRF) is one of the most prominent and under-discussed symptoms of
cancer. 48% of cancer patients experience CRF and 58% to 94% of
patients with breast cancer experience CRF while they are undergoing treatment
(1). The National
Comprehensive Cancer Network defines CRF as “a
distressing persistent, subjective sense of physical, emotional and/or
cognitive tiredness or exhaustion related to cancer or cancer treatment that is
not proportional to recent activity and interferes with usual functioning” (2). Due to the persistent sense of tiredness unrelated to activity,
patients often describe
feeling paralyzed by CRF, as it interferes significantly with their quality of
life. What I found fascinating was symptoms of CRF could be present after the
cancer has been treated up until death, meaning something about the cancer, treatment,
or both, caused a long-lasting, if not permanent change in the patient on a
molecular level (1). It is also worth noting that breast cancer patients who
received chemotherapy and radiation versus radiation alone were more likely to
be fatigued years after treatment, showing the type of therapy most definitely
influences the duration and severity of CRF (1).
In a way, CRF
mirrors cancer. Although a common term, its causes are not well known and it
does not stem from a single or direct source. Our current understanding of CRF
suggests that it is brought on via a multitude of factors, just as cancer is.
The web-like interactions between the numerous factors that cause CRF make it
extremely complex and difficult to define. In recent years, health
professionals have been trying to more strictly define CRF as well as create a
universal scale and develop clearer guidelines that will illustrate its
severity in a patient. This will also allow data to be compared with better
accuracy in hopes to improve success with treatment and overall knowledge of
CRF. I created a chart showing what are thought to be the top contributors to
CRF and how they influence one another. Although the interactions are more
complex than what I have shown, the diagram encompasses the general idea.
This article
discusses several hypotheses and treatment options/potential treatments for CRF
in breast cancer patients but I wanted to focus on one particular hypothesis,
which supports the idea that exercises can help combat the debilitating
symptoms of CRF. This hypothesis ties into one of the newer hallmarks of cancer
that we have not discussed in much detail, ‘Deregulating Cellular Energetics’.
It states, “CRF…may reflect disordered mitochondrial biogenesis, which upsets the
balance between aerobic and anaerobic metabolism” (1). Tumor cells, unlike
normal cells, have the ability to proliferate under hypoxic conditions – they
rely on anaerobic glycolysis versus oxidative phosphorylation, the preferred
pathway for muscle tissues (3).
Anaerobic Respiration: Oxygen is not required
C6H12O6 + (2) C3H6O3
(lactic acid) + (2) ATP
Aerobic Respiration: Oxygen is required
C6H12O6 + O2 + CO2 + H2O + (38) ATP
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2849637/figure/F1/ |
Without oxygen, cancer cells are able to enter this glycolytic pathway,
which produces lactic acid and a very minimal amount of ATP (1/19th
the amount), depriving the normal muscle tissues of adequate levels of ATP, hence
the lack of energy patients experience with CRF (4). This is a huge advantage for
cancer cells because as the cells proliferate, the tumor environment becomes
more hypoxic and thus the cells must be able to adapt to the conditions in
order to thrive.
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| http://stke.sciencemag.org/cgi/content/full/sci;324/5930/1029/F2 |
How are they able to do this?
One of the ways cancer cells are able to survive under hypoxic
conditions is due to the activation of the hypoxia-inducible
factor gene (HIF). HIF is a heterodimer that is activated under hypoxic
conditions. HIF induces a multitude of genes that lead to the modification of
many cellular functions, allowing cancer cells to proliferate under conditions
where normal cells would die (3).
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| http://accessscience.com/loadBinary.aspx?filename=YB071150FG0010.gif |
This cellular energetics-based hypothesis infers
that muscle tissues are deprived of ATP as a result of the tumors use of
anaerobic metabolism; it is essentially based on the idea that there is an
imbalance of aerobic and anaerobic metabolism that is created in the presence
of breast cancer (1).
Muscles are full
of mitochondria, which is where the Krebs cycle takes place. In glycolysis, pyruvate enters the mitochondria and undergoes oxidation,
resulting in ATP as a product.
ATP is energy that allows for protein synthesis to take place. Therefore a lack
of ATP leads to in the “diminution of muscle biosynthesis” and impacts
cardiac performance (1).
The Benefits
of Exercise for Breast Cancer Patients with CRF
According to
this hypothesis, the problem is that cardiac performance is negatively impacted
due to the lack of muscle biosynthesis. This stems from the mitochondria being
unable to produce as much ATP for protein synthesis. The idea behind exercising
aiding in CRF treatment is that “resistance training or aerobic exercise stimulates
mitochondrial biogenesis” and will thus lead to increased production of ATP and
proteins (1).
Exercise is known specifically to help regulate sleep, mood, and
cortisol levels (a hormone released in higher levels during periods of stress that
also aids in fat, protein and carbohydrate
metabolism). These are all critical targets in patients experiencing CRF. Just
improving ones sleep can alleviate psychological disturbances, mood, and some
comorbid conditions. Furthermore, exercising helps combat obesity, which
increases the likelihood of breast cancer recurrence (1).
Other Treatments
Since CRF causes a whole host of symptoms, there are many ways it is
treated. The book, Putting Evidence Into Practice, contains an entire chapter on fatigue and the effect of certain treatments.
These treatments range from massage, relaxation, healing touch, behavioral
techniques, exercise, to pharmacological treatments (5).
Problems Arising from CRF Treatment
As mentioned several times previously, there is no direct cause of CRF
and many factors influence its severity and onset. Therefore, each patient must
be considered on an individual basis. I imagine the future of CRF treatment
being similar to personalized medicine and targeted drug therapy. What I see
needing to be to be taken into account in treatment is:
Age/Gender
Type of cancer
Stage of cancer
Date of diagnosis
Recurrence of cancer (1st or 2nd time having it
etc.)
Type and duration of treatment
Past medical history
Current conditions (medical or psychological)
Current medications
General lifestyle (profession, levels of activity, diet, weight, etc.)
Family history
Thinking about this reminded me of Kate Loranger’s lecture on her
profession as a genetic counselor. CRF seems like a significant enough
condition to where a specialized profession specifically dedicated to treating
patients suffering from it would be extremely beneficial. Just like a genetic
counselor, they would spend a long time getting to know the patient in detail
and from there would decide the best course of treatment and monitor them along
the way. Right now, doctors are the ones treating patients with CRF however it
seems as though the condition calls for much more personalized attention. Perhaps
it could be a profession available to those who have gone through medical
school and would then require an additional amount of training. These
specialists would not only be skilled in medicine and diagnosis, but also in
psychological treatments like a genetic counselor. From my knowledge of CRF,
the psychological part is an incredibly important area to target. There should
be open communication with not only patients but also their family, friends,
and caregivers so they all can contribute to improving the comfort and quality
of life for the patient.
Thoughts
1.) I liked this article because it helped me gain a better perspective
about what it’s like on an everyday basis to have cancer. We learn a lot about
cancer on the molecular level and can often see the physical symptoms of cancer
like hair loss, but if it has not had a direct impact on your life, it is
difficult to imagine what it’s like to be the patient. I know I often think of
symptoms of cancer as a direct result of chemotherapy and radiation like
nausea, hair loss, and exhaustion but I never really realized the stress and
fatigue patients constantly experience even after they have been treated.
2.) After reading this, I was surprised by the percentage of people who
suffer from CRF without treatment success. Modern day medicine is so advanced
it seems we can treat almost anything. Many of the symptoms of CRF also mimic
those of chronic fatigue or depression, which we can typically treat with
success, so it is interesting that so many people still suffer from it.
