Ein mikroskopischer Blick auf eine unbesiegte Krankheit: Darmkrebszelle mit genetisch veränderten Bakterien Bild: dpa
Appetitlosigkeit und Abmagerung gehören zu den verheerenden Folgen von Krebserkrankungen. Wie funktionieren diese zerstörerischen Mechanismen auf molekularer Ebene?
Beating cancer is not easy, ask anyone who has survived. It is a war. Cancer is often now thought of as a chronic disease – a long, drawn out conflict. As in most chronic diseases, a loss of appetite accompanies the patient’s journey. When this loss of appetite becomes a major contributor to the deterioration of one’s nutritional status and quality of life, therein lies the collateral damage.
Many acute and chronic diseases are associated with the loss of appetite, which is termed “anorexia”, which should be not confused with the psychiatric syndrome of anorexia nervosa. In acute illnesses, the anorexia may persist only for a few days without a significant impact on body weight.
The Derangement Of Brain Neurochemistry
Appetite is a potent drive of human behaviour and it should not be surprising that appetite is tightly controlled by many different and often opposing ways. Clearly, the development of anorexia has a negative psychological impact, e.g. on the cancer patient’s perception of their health, but since it is also accompanied by the loss of muscle and necessary adipose tissue, its role in promoting weight loss needs to be better understood. This additional contribution to rapid weight loss is termed “cachexia”.
Cancer patients usually have both anorexia and cachexia. This anorexia-cachexia syndrome is a debilitating clinical condition which is characterized by many symptoms, including reduced appetite, changes in taste and smell, and early satiety (“sense of fullness”). There are many factors in the development of the syndrome. At the molecular level, the main feature is the derangement of brain neurochemistry controlling energy intake and energy use, inducing severe alterations in the metabolism of peripheral tissues (e.g. muscles, adipose tissue, liver). In advanced cancer patients, the anorexia-cachexia syndrome becomes detrimental since it affects organ and tissue function, leading to early death.
Producing Signals That Lead To Satiety
Until now, the research has always been separated into the pathological aspects of the anorexic symptoms (i.e. brain neurochemical alterations) or the metabolic derangements (particularly muscle loss). Recent data suggest that the abnormal neurochemical activity may actually contribute to the changes in metabolism of peripheral tissues, in addition to its known role in triggering the onset of anorexia.
Thus, common aspects may exist between the anorexic and cachexic symptoms. Mounting evidence indicates that the hypothalamus, an area located at the base of the brain, may be a key player in setting off anorexia and cachexia. During tumour growth, the main controller of the feeling of satiety – the hypothalamic melanocortin system – is overstimulated and the pathological and persistent form of satiety, i.e. anorexia, develops.
Chasing the Gene-Variations Responsible
Furthermore, the hyperactivity of these melanocortin neurons is triggered by the beginning of an inflammatory response, the same one that is the “physiological” response to the growing tumour. When the human body activates its immune system to fight the growing tumour with these proinflammatory “weapons” called cytokines, the result may cause collateral damage. Thus, the altered eating behaviour and tissue metabolism may be a result of the body’s war against the cancer.
My colleagues and I now know much more about the molecular events that occur in anorexia-cachexia syndrome. In particular, I have been studying the role of brain neurotransmitters in the development of this syndrome. I feel that one major obstacle remains to understand how genetics play a part.
I strongly think that the different symptoms of the anorexia-cachexia syndrome are directly related to the variations of several genes, which in turn, change the individual’s neurochemical and metabolic response to similar challenges. In the near future, I will be chasing the genes associated with the onset of anorexia-cachexia in cancer patients. Hopefully, the identification of genetic variations will allow prediction of the development of anorexia and cachexia, and thus, we as physicians, can use strategies that prevent or minimize the collateral damage.
Basic and clinical research is a tough adventure, with many sleeping hours lost by checking patients’ vital signs or measuring molecules in blood whose existence is unknown to 99% of the world population. Yet, there is a marvellous feeling of unfinished business when you complete an experiment and you then want to know more. Many times I play with my friends at dreaming in which times we would have loved to live in. Some of us wanted to live during the French Revolution, others would prefer the Roman Empire.
My dream is to live in interesting times – times where we are challenged every day by problems urging a solution. My daily life provides me with clinical and scientific challenges, but because of my work and the results obtained with my colleagues, I feel as I am part of a global movement to improve the quality of human life. Therefore, if someone wishes me “May you live in interesting times”, I always reply “Thank you, I am living in interesting times.”
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