In this response to a letter to the editor (Clin Cancer Res 2016;22:2595), which was published in the May 15, 2016, issue of Clinical Cancer Research (1), quotation marks were appropriately used around points 1–4, but mistakenly omitted from points 5 and 6. This omission may have caused confusion for the reader, who would be unable to differentiate between the text quoted from the letter to the editor by Leon and colleagues and the authors' responses. Points 5 and 6 are correctly listed below. The authors regret this omission.
Point 5: “Finally, according to NCBI-AceView, the mouse Rrm1 gene is expressed at a very high level, and might differ from RRM1 in different tissue types, influencing the results in the in vivo models.”
RRM1 is expressed at a high level in the mouse, and this might affect tissue types differentially compared with the human. In in vivo studies reported in our article, we investigated the effects of pimasertib and gemcitabine on the expression of several genes, including RRM1 in an orthotopic model. We did not assess the effects of RRM1 on different tissues, as this was not the remit of the study. Clearly, this is a critique that can be made for all in vivo studies and underscores the importance of clinical trials that measure RRM1. Assessing the effects on "different tissue types" in human studies would clearly be challenging.
Point 6: “We believe that additional analyses/models are needed to determine the role of RRM1 modulation by pimasertib on gemcitabine sensitivity before it can be used for innovative clinical strategies.”
Although we agree about the need for additional analyses and models, we cannot understand this specific point as innovative clinical strategies will stem from well-designed preclinical studies.
- ©2016 American Association for Cancer Research.