Short abstract with Stephan Herzig. [Helmholtz Zentrum München]
Cancer often results in weight loss due to unwanted metabolic complications. This so-called cancer cachexia is accompanied by a poor prognosis with regard to disease progression, quality of life, and mortality. After sepsis, cachexia is the most frequent cause of death in cancer patients. It is not entirely clear which biochemical mechanisms play a role. To date there have also not been any pharmacological possibilities for selectively influencing tumor-associated wasting syndrome.
Now, scientists at the Institute for Diabetes and Cancer (IDC) at Helmholtz Zentrum München say they have identified the adenosine monophosphate (AMP)-activated protein kinase (AMPK) as the central enzyme in cancer cachexia. AMPK is normally responsible for protecting cells from energy deficiency. In the case of cancer cachexia, however, AMPK activity is inhibited due to the illness, resulting in a pointless waste of the body's own energy store. Their study (“An AMP-Activated Protein Kinase–Stabilizing Peptide Ameliorates Adipose Tissue Wasting in Cancer Cachexia in Mice”) appears in Nature Medicine.
Selective AMPK reactivation was successfully carried out in tumor models. The therapeutic manipulation took place through a specific peptide that prevents the interaction between AMPK and the lipid droplet-associated protein Cidea, and consequently can stop the increased fat breakdown found in tumor diseases.
“We developed an Ampk-stabilizing peptide, ACIP, which was able to ameliorate WAT [white adipose tissue] wasting in vitro and in vivo by shielding the Cidea-targeted interaction surface on Ampk,” write the researchers. “Thus, our data establish the Ucp1 [uncoupling protein 1]-independent remodeling of adipocyte lipid homeostasis as a key event in tumor-induced WAT wasting, and we propose the ACIP-dependent preservation of Ampk integrity in the WAT as a concept in future therapies for cachexia.”
“Our data suggest that the preservation of 'healthy' adipose tissue can promote not only the quality of life, but also the response to treatment and the survival of cancer patients,” says Prof. Stephan Herzig, IDC Director. “The interaction between AMPK and Cidea can be taken as a starting point for developing new lipolysis inhibitors which could then prevent the breakdown of energy stores in the fat of tumor patients.
The professor also sees possibilities for transferring the acquired insights to other wasting disorders, such as with sepsis or burn injuries.