Cancer metastasis, the process by which tumour cells spread throughout the body and form secondary tumours at distant sites, is the leading cause of cancer-related deaths. The metastatic cascade is a highly complex process encompassing initial dissemination from the primary tumour, travel through the blood stream or lymphatic system, and the colonisation of distant organs. However, the factors enabling cells to survive this stressful process and adapt to new microenvironments are not fully characterised. Drosophila have proven a powerful system in which to study this process, despite important caveats such as their open circulatory system and lack of adaptive immune system. Historically, larvae have been used to model cancer due to the presence of pools of proliferating cells in which tumours can be induced, and transplanting these larval tumours into adult hosts has enabled tumour growth to be monitored over longer periods. More recently, thanks largely to the discovery that there are stem cells in the adult midgut, adult models have been developed. We focus this review on the development of different Drosophila models of metastasis and how they have contributed to our understanding of important factors determining metastatic potential, including signalling pathways, the immune system and the microenvironment.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterised by the death of motor neurons leading to paralysis and death generally 3–5 years post-symptom onset. ALS is a cell- and non-cell-autonomous disease, with glia such as astrocytes influencing disease pathology and progression. Our laboratory has previously identified purine metabolism dysfunction in induced neural progenitor cell-derived astrocytes (iAstrocytes) from sporadic ALS (SALS) cases, driven by loss of the enzyme adenosine deaminase (ADA). Here, we have demonstrated that loss of ADA, along with changes to ecto-5′-nucleotidase and hypoxanthine-guanine phosphoribosyl transferase led to disruption in purine metabolite levels, linked to the level of the ADA enzyme. These alterations were recapitulated in SALS CSF and post-mortem tissue, with ageing and sex affecting purine metabolite levels downstream of ADA and positively correlating with disease progression. Loss of ADA led to reduced 53BP1-mediated DNA repair and increased P16 levels, which was recapitulated in control iAstrocytes via ADA inhibition. Our findings indicate that TDP43 dysfunction drives impairment of ADA-mediated purine metabolism in vitro, leading to downstream effects that include DNA damage, likely through inhibition of DNA repair mechanisms, and the induction of cellular senescence. Furthermore, these results suggest that therapeutic targeting of the ADA pathway may help slow ALS disease progression.