Wednesday, November 28, 2012

SeeMyScience: What is Cancer Cachexia?

When I completed my Bachelor of Science, I was looking for a lab in which to complete my one-year honours qualification. Dr Lewandowski had been one of my lecturers during my undergrad, and his group had started working on an serious condition of muscle loss experienced by many chronic disease patients, called ‘cachexia’. In Part 2 of "See My Science", I'll begin to explain what cachexia is, and why researching it is important.

Cachexia, affecting 50% of cancer patients, causes extreme loss of muscle and fat (Source)


What is Cachexia?

Cancer Cachexia (pronounced car-kex-ear) is the unintentional loss of muscle and fat that occurs in many patients with cancer. While cachexia is seen in several other diseases, such as HIV/AIDS, sepsis, chronic obstructive pulmonary disease and congestive heart failure, the loss of muscle has been shown to occur most rapidly in cancer patients

Patients are said to have “[…] a complex metabolic profile […]”, meaning that there are many changes in their metabolism which are causing these issues, resulting in more energy being used by the body than is being put in/stored. This also means that the metabolism of muscle is altered, i.e. the rate of muscle break-down is faster than the rate of creation of new muscle. Part of this is in response to the increased energy demand (the body can break down muscle in order to obtain more energy), but it is also caused by complex chain reactions  triggered by the body’s response to the tumour. This is just one example of a pathway involved.

Patients with cachexia have a lower quality of life than patients who do not lose weight, experiencing greater pain, fatigue, and reduced mobility as muscles become less functional. Weight-loss also reduces the effectiveness of chemotherapy, with cachectic patients having to have lower doses, for shorter periods, and often unable to undergo as many rounds of therapy. Developing an effective treatment for cachexia would help cancer patients to have a better quality of life, and also help improve their chances of successful therapy.

The most common definition used at present is involuntary weight loss of greater than 5% from historical weight, a body mass index (BMI) less than 20 with any degree of weight loss greater than 2%. However, these measures only take into account weight, ignoring the vast number of other serious symptoms. Therefore, newer definitions are supported by other symptoms, including inflammation, fatigue, and decreased quality of life. See Fearon et al 2011 for the consensus definition.

How common is Cachexia?

It is generally thought that about half of all cancer patients will develop cachexia, although this can rise to as much as 80% in the later stages of cancer. In is most common in cancers of the pancreas, colon and lung. 45% of patients with cachexia lose more than 10% of their original body weight, and patients who lose 30% of their original body weight will unfortunately usually succumb, with around 20% of cancer-related deaths thought to be attributable to cachexia.

Despite how common cachexia is, it is often underdiagnosed. This may be because weight-loss is seen as an inevitable part of cancer. Sometimes it is also because the tumour itself it considered more urgent than the loss of weight. Weight-loss is also often thought to be a side-effect of cancer therapy, and while this is true to a certain extent, many cancer patients lose weight prior to undergoing chemo or radiation, or even before they receive a diagnosis.

Why don’t they just eat more?

Unlike some forms of weight-loss, simply eating more does not cure cachexia. Neither does smoking pot, sorry. Improving nutrition is vitally important to the treatment of cachexia (you can’t make muscle out of thin air!), but alone, it is not enough, because reduced calorie intake is not the underlying cause. This is because of those complex pathways I mentioned before, which are telling the body to break down muscle and fat. We need to stop the processes that cause the body to break down muscle, but in the past, this has proven to be very difficult due to the complexity of the condition.

I like to think of it like a busy city. You might have a normal route you take from your house to work. One day, a tree falls across the road, and you can’t get by. What do you do? Back-track, and take another route! The body can to the same thing: you stop one pathway, only for another to compensate. The only way you’re not getting to work is if every street, railroad and back alley is impassable. In order to stop cachexia, we have to hit it in lots of different places. This is called a multi-target approach, which I will discuss in a few post’s time, but generally, it will involve improving nutrition, targeted exercise, and a combination of pharmaceuticals that will inhibit some things and promote others.

At present, we do not have a globally effective treatment for cancer cachexia. There are some treatments that may work for some people, but not others. The aim of our study was to look at two potential treatments, both alone and in combination, to figure out whether they were able to slow down, or even stop, the loss of muscle we see in cachexia.

Next post, I’ll be explaining the pathways my research focuses on, and how they interact with the body. In the mean-time, is there anything you would like to know about cachexia that I haven’t covered here? I’d love to hear from you, so either leave a message below, or drop me a line.


See My Science” aims to explain the science done by our group in a manner accessible to the public. The current series focuses on the following publication: Vaughan VC et al (2012) Eicosapentaenoic Acid and Oxypurinol in the Treatment of Muscle Wasting in a Mouse Model of Cancer Cachexia. PLoS ONE 7(9): e45900. doi:10.1371/journal.pone.0045900

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