Searching for the Ideal Therapy for Cancer Cachexia

Abstract

EditorialAlthough megestrol acetate and corticosteroids have been, and still are, the universal drug approaches for the treatment of the cancer cachectic syndrome, novel drugs and treatments have lead to promising approaches to counteract wasting thus improving the quality of life and, possibly, survival of cancer patients. Thus, ghrelin agonists, such as anamorelin, that basically act on food intake, nonsteroidal selective androgen receptor modulators (SARMs), such as enobosarm, hold promise as a new class of anabolic therapies for cancer patients that manifest muscle wasting. In addition, betablockers can reduce body energy expenditure and improve efficiency of substrate utilization. Some of them do combine many different pharmacological effects. For instance, espindolol is a non-specific β1/ β2 adrenergic receptor antagonist that exhibits effects through β and central 5-HT1α receptors to demonstrate pro-anabolic, anti-catabolic, and appetite-stimulating actions. Finally, myostatin antagonists, such as bimagrumab or BYM338, seems to be able in pre-clinical models to prevent skeletal muscle mass loss and preserve muscle function facilitating the recovery from muscle atrophy. All of the commented drugs are certainly new promising strategies to fight cancer cachexia [1].However, in order to improve the treatment of cancer cachexia, several considerations have to be made. First, a better understanding of the pathophysiological mechanisms related to skeletal muscle and, in general, body wasting, will enable the development of novel therapeutic approaches. Second, more research should also be devoted to biomarkers for cancer cachexia. Indeed, in many clinical centres, cancer cachexia is treated only when a significant amount of weight loss is detected, or when the patients suffer from certain limitations in daily living activities. Biomarkers could detect the changes before any clinical manifestations arouse, facilitating treatment and, possibly, improving prognosis. Progress has certainly been made concerning biomarkers [2] but more research is needed in this field to find an easy measurable --either blood or urine present and specific muscle wasting biomarker. Third, since cancer cachexia leads to decrease potential for muscle regeneration due to the fact that satellite cells are not able to differentiate into myocells, one new revolutionary concept that will, no doubt, involve further research is that of cell reprogramming to muscle. Therefore, future studies are needed on the potential of stem cell therapy to overcome the problem of muscle cell regeneration. While adult stem cells are tissue-specific and have limited capacity to be expanded ex-vivo, pluripotent stem cells, have the capacity to differentiate into any cell type while possessing unlimited in vitro selfrenewal. Scott et al.[3] described a methodology for large-scale isolation of satellite cells from skeletal muscle. This could then be applied as a therapeutic strategy to stimulate muscle regeneration. Fourth, it is quite clear that a single drug tre...