Erdem Bangi and colleagues demonstrate a new approach to developing personalized therapy for a patient with treatment-resistant colorectal cancer: using a fruit fly genetically modified with a patient's own cancer mutations to test candidate treatments. Like many people with metastatic colorectal cancer, especially those involving RAS genetic mutations, the patient treated by Bangi et al. had exhausted most treatment options. To look for new possibilities, the researchers analyzed the genomic landscape of the patient's tumors, identifying nine key gene changes that appeared to be driving the cancer. They altered the genome of a Drosophila fruit fly to contain these genetic changes and tested a battery of drugs in these Drosophila to determine which drugs prolonged survival. Their technique identified a combination of the chemotherapy drug trametinib and a bisphosphonate drug called zoledronate, used most often to prevent skeletal fractures, as a candidate treatment. The patient's new treatment with the two drugs reduced targeted tumors and kept them stable for 11 months.
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Science Advances