Drosophila Larval Models of Invasive Tumorigenesis for In Vivo Studies on Tumour/Peripheral Host Tissue Interactions during Cancer Cachexia

Int J Mol Sci. 2021 Aug 2;22(15):8317. doi: 10.3390/ijms22158317.


Cancer cachexia is a common deleterious paraneoplastic syndrome that represents an area of unmet clinical need, partly due to its poorly understood aetiology and complex multifactorial nature. We have interrogated multiple genetically defined larval Drosophila models of tumourigenesis against key features of human cancer cachexia. Our results indicate that cachectic tissue wasting is dependent on the genetic characteristics of the tumour and demonstrate that host malnutrition or tumour burden are not sufficient to drive wasting. We show that JAK/STAT and TNF-α/Egr signalling are elevated in cachectic muscle and promote tissue wasting. Furthermore, we introduce a dual driver system that allows independent genetic manipulation of tumour and host skeletal muscle. Overall, we present a novel Drosophila larval paradigm to study tumour/host tissue crosstalk in vivo, which may contribute to future research in cancer cachexia and impact the design of therapeutic approaches for this pathology.

Keywords: Drosophila larvae; Ras; Scribble; cancer cachexia; dual driver system.

MeSH terms

  • Animals
  • Cachexia / etiology
  • Cachexia / metabolism
  • Cachexia / pathology*
  • Carcinogenesis / genetics
  • Carcinogenesis / metabolism
  • Carcinogenesis / pathology*
  • Disease Models, Animal*
  • Drosophila
  • Gene Expression Profiling
  • Humans
  • Janus Kinases / genetics
  • Janus Kinases / metabolism
  • Larva / genetics
  • Larva / growth & development*
  • Larva / metabolism
  • Neoplasms / complications*
  • STAT3 Transcription Factor / genetics
  • STAT3 Transcription Factor / metabolism
  • Signal Transduction


  • STAT3 Transcription Factor
  • Janus Kinases