Functional Exploration of African Colorectal Cancer Patients Using Personalised Drosophila Avatars

Abstract Colorectal cancer across sub-Saharan Africa presents a growing global health burden, with increasing cases and mortality linked to late diagnosis, limited healthcare access and lack of effective treatments. African patients typically present with aggressive disease marked by distinct genomic signatures, indicating the need for targeted treatment approaches. We integrated genetic modelling, phenotypic scoring, imaging and biochemical analysis to explore how mutations found in individual Nigerian colorectal cancer patients influence drug responsiveness. We used the data from Cancer Genome Atlas to identify mutation profiles specific to Nigerian patients. We then generated ten stable Drosophila melanogaster personalised patient avatar lines designed to model patient genomic profiles. This study focused on three lines; each line included oncogenic RAS plus targeting patient-specific variants. These models exhibited various phenotypes including altered larval size, gut size and reduced survival. Two of the three avatar lines showed improved survival, reduced hindgut proliferation zone expansion and restored redox balance after treatment with regorafenib and trametinib. Mirroring clinical patient responses, we found that response to therapy is dependent on the specific genetic profile of the tumour. African colorectal cancer showed distinct mutation patterns that contribute to tumour heterogeneity. Patient-derived Drosophila avatars were engineered using tumour-specific genetic mutations with key features of human colorectal cancer. Treatment with targeted therapies showed responses patterned by tumour genotype. Response patterns indicated the need for personalised for colorectal cancer therapies among diverse populations. Competing Interest Statement The authors have declared no competing interest.