Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.07.24.219907v1?rss=1 Authors: Gross, S. M., Sanchez-Aguila, C., Zhan, P. J., Heiser, L. M. Abstract: Understanding the molecular basis for drug-induced changes in cellular responses is critical for the identification of effective cancer treatments. Measurement of endpoint viability across a range of drug doses is the standard approach to quantify drug efficacy. While informative, this read-out does not account for the multiple cell fate decisions individual cancer cells undergo in response to drug treatment. As a consequence, the basis for drug-induced changes in cell numbers remains poorly defined. To evaluate the impact of cancer drugs on individual cells, we engineered AU565 breast cancer cells to express a fluorescent cell cycle reporter and then assessed dynamic responses to a panel of drugs. Detailed population and single cell analyses revealed heterogeneous drug-, dose-, and time-dependent effects on cell cycle durations and cell fates. Lapatinib induced dose-dependent extension of G1 duration and limited apoptosis. In contrast, cell fate responses varied with gemcitabine dose: low gemcitabine doses induced extension of S-G2 durations, whereas high doses induced apoptosis after prolonged exposure. Lastly, paclitaxel induced apoptosis and caused only modest cell cycle effects. Overall, our analyses revealed that each drug induced distinct impacts on cell fate that were dependent on the dose and duration of treatment. Understanding these differences has implications for the mechanisms of therapeutic resistance and the identification of effective drug combinations and treatment schedules. Copy rights belong to original authors. Visit the link for more info