Natural diversity facilitates the discovery of conserved chemotherapeutic response mechanisms

Individuals within the human population vary in their responses to antineoplastic drugs based on their genetic background. Five unique human, Caenorhabditis elegans, and Drosophila melanogaster genetic backgrounds with variable drug responses are represented above with different colors. The identification of specific genetic differences within the human population that underlie variable drug responses is a central goal of modern medicine, but remains challenging because of the highly heterogeneous human genome and lack of tractability of human studies. However, recent studies have shown that there is substantial variability in antineoplastic drug responses among individuals within the classic invertebrate species C. elegans and D. melanogaster. The conservation of variable antineoplastic drug responses in these model species suggests that common mechanisms may be affected by genetic differences within each species. We argue the tractability of these systems will enable the identification of specific genetic variants that underlie variable drug responses.