It is increasingly recognized that cellular responses to their environment are shaped not only by their genetic composition but also by the properties of their neighbouring cells. A notable example is cell competition, an evolutionarily conserved process found in organisms ranging from Drosophila to humans [1]. In this process, less fit cells, referred to as “loser cells,” are eliminated by their fitter neighbours, known as “winner cells,” thereby preserving the overall health of the tissue [2]. Over the past decade, an emerging theme in tissue interactions has been the communication between distant organs, referred to as inter-organ crosstalk [3]. Secreted factors are essential mediators of this crosstalk. Proteomic analysis of human serum has identified elevated levels of secreted proteins, such as GDF15, as being linked to various pathological conditions, including brain aging, obesity, and cancer [4]. Moreover, neutralizing antibodies targeting GDF15 have recently shown great promise in managing systemic conditions like cancer cachexia [5]. Inter-organ crosstalk similarly plays a critical role in development and is involved in processes including the coordinated growth and maturation of multiple organs [6] and the prioritization of brain growth under nutrient restriction [7].

This review explores recent progress in understanding how organs compete and redistribute resources under metabolic stress, emphasizing studies conducted in the fruit fly Drosophila, a powerful genetically tractable model system for studying inter-organ communication. Understanding how the organ hierarchy is established during development and in cancer—a process we term “organ competition”, is highly relevant in developmental biology and cancer biology. The comparison in organ fitness ensures that privileged organs can grow at the expense of less critical tissues under metabolic stress during development. Similarly, these mechanisms also contribute to fuelling tumour growth in cancer.