The Power of Drosophila in Modeling Cancer Cachexia

Late-stage cancer patients often exhibit cachexia, a wasting syndrome characterized by the loss of muscle and adipose tissues. However, the extent to which these wasting effects directly contribute to mortality remains unclear. Drosophila, a well-conserved model organism, has been instrumental in demonstrating systemic energy wasting and mortality in the context of tumors, similar to mice and humans. Research in Drosophila has elucidated the underlying mechanisms by which tumor-associated secreted proteins cause muscle atrophy and lipid loss, ultimately leading to energy wasting. Nevertheless, emerging evidence in both Drosophila and mammals challenges the notion that blocking energy loss in muscle or fat is sufficient to improve tumor-associated mortality, suggesting the existence of additional pathogenic factors in cancer cachexia. This raises two critical questions: how do tumors disrupt the physiological functions of other organs besides muscle and fat, and to what extent do these organ dysfunctions contribute to tumor-induced mortality? In this chapter, we summarize current knowledge regarding how fly tumors interact with host organs or tissues through the production of cachectic secreted proteins, and how they influence disease progression. We also discuss the power of Drosophila models in uncovering the mechanisms and principles of tumor-induced wasting and mortality and exploring therapeutic opportunities using various leading technologies.