Functional Exploration of African Colorectal Cancer Patients Using Personalised Drosophila Avatars

Area of Science:

• Oncology
• Genomics
• Pharmacology

Background:

• Colorectal cancer (CRC) in sub-Saharan Africa is a growing health concern, characterized by late diagnoses and aggressive disease with unique genomic profiles.
• Effective targeted treatments are lacking for African CRC patients, necessitating research into personalized therapeutic strategies.

Purpose of the Study:

• To investigate how specific genetic mutations in Nigerian colorectal cancer patients influence drug responsiveness.
• To develop and utilize personalized patient avatar models for predicting treatment outcomes.

Main Methods:

• Integrated genetic modeling, phenotypic scoring, imaging, and biochemical analysis.
• Utilized Cancer Genome Atlas data to identify Nigerian CRC mutation profiles.
• Generated personalized *Drosophila melanogaster* (fruit fly) avatar lines to model patient-specific genomic profiles, focusing on oncogenic RAS and patient variants.

Main Results:

• Three avatar lines exhibited phenotypes such as altered larval and gut size, and reduced survival.
• Two of the three avatar lines demonstrated improved survival, reduced hindgut proliferation, and restored redox balance upon treatment with regorafenib and trametinib.
• Therapeutic response was found to be dependent on the specific genetic profile of the tumor, mirroring clinical observations.

Conclusions:

• Personalized *Drosophila melanogaster* models can effectively recapitulate patient-specific colorectal cancer characteristics and drug responses.
• Targeted therapies, such as regorafenib and trametinib, show potential efficacy in specific patient subgroups based on their genomic profiles.
• This approach highlights the importance of genetic profiling for tailoring colorectal cancer treatment in sub-Saharan African populations.