Personalizing cancer patient drugs using flies
Cancers are one of the main causes of death in industrialized societies. Incidence of thyroid cancers has tripled in the last decades, making it one of the more prominent type of cancer. Most of these cancers are papillary thyroid carcinomas, for which there is a 98% survival rate over 5 years. However, there are other, less treatable forms, that give only a 50% survival rate of over 5 years.
In a recently published study (Levinson and Cagan, 2016) from Ross Cagan’s laboratory at the Icahn School of Medicine at Mount Sinai, NY, Levison and Cagan investigate the roles of different mutations to a gene named RET and the role of these mutations in the initiation and progression of cancer. In order to do so, the authors inserted variants of human RET genes into fruit flies. They inserted either CCDC6-RET, which is associated with benign thyroid tumors, or NCOA4-RET which is associated with the more aggressive form.
The authors first found that these 2 mutants activated different proteins downstream of their activity, and then tested a panel of 55 FDA approved drugs to block these cancers. They found that only 5 drugs inhibited the benign form, and that 5 drugs inhibited the more aggressive form. Only 3 drugs inhibited both forms of this cancer. Interestingly, drugs that were not anticipated to block the cancer, according to previous data, were also effective. This effect was due to the drugs being effective not against the RET protein itself, but against other factors contributing to the cancer progression (off target effects). Conversely, drugs previously shown to suppress these cancers were ineffective. This experiment thus showed that drug interactions and off target effects are important. The authors also tried administering 2 drugs at once, and found that several drugs interacted synergistically in suppressing cancer growth.
Overall, this study showed the efficacy of a fly tumor model in finding personalized therapeutic drugs to fight cancer. This is an powerful approach since this assay can be done relatively quickly in large numbers of flies at a low cost. These results can be used to integrate knowledge obtained through other systems, such as human cells or other mammalian model organisms, for identifying appropriate mixes drugs to help fight cancer better.
Citation: Levinson, S. and Cagan, R. L. (2016) ‘Drosophila Cancer Models Identify Functional Differences between Ret Fusions’, Cell Reports. The Authors, 16(11), pp. 3052–3061. doi: 10.1016/j.celrep.2016.08.019.
In a recently published study (Levinson and Cagan, 2016) from Ross Cagan’s laboratory at the Icahn School of Medicine at Mount Sinai, NY, Levison and Cagan investigate the roles of different mutations to a gene named RET and the role of these mutations in the initiation and progression of cancer. In order to do so, the authors inserted variants of human RET genes into fruit flies. They inserted either CCDC6-RET, which is associated with benign thyroid tumors, or NCOA4-RET which is associated with the more aggressive form.
The authors first found that these 2 mutants activated different proteins downstream of their activity, and then tested a panel of 55 FDA approved drugs to block these cancers. They found that only 5 drugs inhibited the benign form, and that 5 drugs inhibited the more aggressive form. Only 3 drugs inhibited both forms of this cancer. Interestingly, drugs that were not anticipated to block the cancer, according to previous data, were also effective. This effect was due to the drugs being effective not against the RET protein itself, but against other factors contributing to the cancer progression (off target effects). Conversely, drugs previously shown to suppress these cancers were ineffective. This experiment thus showed that drug interactions and off target effects are important. The authors also tried administering 2 drugs at once, and found that several drugs interacted synergistically in suppressing cancer growth.
Overall, this study showed the efficacy of a fly tumor model in finding personalized therapeutic drugs to fight cancer. This is an powerful approach since this assay can be done relatively quickly in large numbers of flies at a low cost. These results can be used to integrate knowledge obtained through other systems, such as human cells or other mammalian model organisms, for identifying appropriate mixes drugs to help fight cancer better.
Citation: Levinson, S. and Cagan, R. L. (2016) ‘Drosophila Cancer Models Identify Functional Differences between Ret Fusions’, Cell Reports. The Authors, 16(11), pp. 3052–3061. doi: 10.1016/j.celrep.2016.08.019.